Long-term Prognosis for Non-functional Neuroendocrine Tumors of the Pancreatic Body and Tail ≤ 3cm

Non Functioning Pancreatic Endocrine Tumor Clinical Trial

Official title:

Long-term Prognosis Comparison Between Parenchyma-sparing and Oncologic Resections for Non-functional Neuroendocrine Tumors of the Pancreatic Body and Tail ≤ 3cm: a Real-world Data Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05907824
• Other study ID #: CSPAC-NEN-5
• Status: Recruiting
• Start date: May 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: September 2023
• Source: Fudan University
• Contact: Xianjun Yu, MD, PhD
• Phone: +86-13801669875
• Email: yuxianjun[@]fudanpci.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to quantify the malignant potential of non-functional neuroendocrine tumors of the pancreatic body and tail ≤ 3 cm by collecting real-world data from large pancreatic centers across the country, and to evaluate the appropriateness of parenchyma-sparing resection and oncologic resection.

Description:

According to epidemiological investigations, the incidence of neuroendocrine tumors has increased 6.4-fold (6.98 per 100,000) . There is controversy in the latest guidelines regarding the management of sporadic non-functional pancreatic neuroendocrine tumors (pNETs) ≤ 2 cm, including follow-up and the choice between parenchyma-sparing resection (PSR) and oncologic resection (OR) . Although pNETs are generally considered indolent tumors, current experience suggests that 9.5%-12.3% of pNETs ≤ 2 cm may have lymph node metastasis, and nearly 20% of resected tumors exhibit one or more invasive features. Awareness of surgical treatment for these patients has been increasing gradually. However, there is no clear recommendation for the choice of surgical approach, and if OR is routinely performed, its prognostic value is unclear and there may be a risk of overtreatment. The advantages of PSR include preservation of both endocrine and exocrine pancreatic function. However, the main oncological limitations of these techniques are inadequate surgical margin clearance and the risk of lack of lymph node dissection. A recent retrospective analysis of prospective databases from four large pancreatic surgery centers showed that for ≤ 3 cm non-functional pNETs, PSR or lymph node-preserving resection had less blood loss, shorter operation time, lower complications rate, and similar long-term oncological outcomes compared to OR. However, this study did not differentiate the tumor locations, as pNETs in the pancreatic head and body/tail have different lymphatic drainage patterns and surgical approaches. Furthermore, the study also showed significant differences in the proportion of PSR and the rate of positive lymph nodes between tumors located in the pancreatic head and those in the body/tail. The ability of existing literature to provide reliable guidelines for pNETs is limited by the low incidence of the disease and short follow-up times. This study aims to quantify the malignant potential of pNETs of the pancreatic body and tail ≤ 3 cm by collecting real-world data from large pancreatic centers across the country, and to evaluate the appropriateness of PSR and OR.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Non-functional neuroendocrine tumors of the pancreatic body and tail = 3 cm.

Exclusion Criteria:

• Presence of liver or distant metastasis.
• Presence of concomitant malignancy.
• Multifocal or recurrent disease.
• Presence of hereditary syndrome (MEN1, VHL, NF).
• Presence of symptoms (specific symptoms of clinical syndromes suspected to be related to excessive secretion of bioactive compounds).
• History of preoperative antitumor therapy.
• Loss to follow-up.

Related Conditions & MeSH terms

• Endocrine Gland Neoplasms
• Neuroendocrine Tumors
• Non Functioning Pancreatic Endocrine Tumor
• Pancreatic Neoplasms

Intervention

Other:
• Histopathological review, long-term prognosis and quality of life follow-up
Histopathological review, long-term prognosis and quality of life follow-up

Locations

Country	Name	City	State
China	Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (5)

Lead Sponsor	Collaborator
Fudan University	First Affiliated Hospital Xi'an Jiaotong University, Qilu Hospital of Shandong University, Southern Medical University, China, The Third Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

References & Publications (13)

Bolm L, Nebbia M, Wei AC, Zureikat AH, Fernandez-Del Castillo C, Zheng J, Pulvirenti A, Javed AA, Sekigami Y, Petruch N, Qadan M, Lillemoe KD, He J, Ferrone CR; PAncreatic Neuroendocrine Disease Alliance (PANDA). Long-term Outcomes of Parenchyma-sparing and Oncologic Resections in Patients With Nonfunctional Pancreatic Neuroendocrine Tumors <3 cm in a Large Multicenter Cohort. Ann Surg. 2022 Sep 1;276(3):522-531. doi: 10.1097/SLA.0000000000005559. Epub 2022 Jun 27. — View Citation

Chivukula SV, Tierney JF, Hertl M, Poirier J, Keutgen XM. Operative resection in early stage pancreatic neuroendocrine tumors in the United States: Are we over- or undertreating patients? Surgery. 2020 Jan;167(1):180-186. doi: 10.1016/j.surg.2019.04.061. Epub 2019 Sep 16. — View Citation

Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, Shih T, Yao JC. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017 Oct 1;3(10):1335-1342. doi: 10.1001/jamaoncol.2017.0589. — View Citation

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. — View Citation

Gratian L, Pura J, Dinan M, Roman S, Reed S, Sosa JA. Impact of extent of surgery on survival in patients with small nonfunctional pancreatic neuroendocrine tumors in the United States. Ann Surg Oncol. 2014 Oct;21(11):3515-21. doi: 10.1245/s10434-014-3769-4. Epub 2014 May 20. — View Citation

Halfdanarson TR, Strosberg JR, Tang L, Bellizzi AM, Bergsland EK, O'Dorisio TM, Halperin DM, Fishbein L, Eads J, Hope TA, Singh S, Salem R, Metz DC, Naraev BG, Reidy-Lagunes DL, Howe JR, Pommier RF, Menda Y, Chan JA. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Pancreatic Neuroendocrine Tumors. Pancreas. 2020 Aug;49(7):863-881. doi: 10.1097/MPA.0000000000001597. — View Citation

Nesti C, Brautigam K, Benavent M, Bernal L, Boharoon H, Botling J, Bouroumeau A, Brcic I, Brunner M, Cadiot G, Camara M, Christ E, Clerici T, Clift AK, Clouston H, Cobianchi L, Cwikla JB, Daskalakis K, Frilling A, Garcia-Carbonero R, Grozinsky-Glasberg S, Hernando J, Hervieu V, Hofland J, Holmager P, Inzani F, Jann H, Jimenez-Fonseca P, Kacmaz E, Kaemmerer D, Kaltsas G, Klimacek B, Knigge U, Kolasinska-Cwikla A, Kolb W, Kos-Kudla B, Kunze CA, Landolfi S, La Rosa S, Lopez CL, Lorenz K, Matter M, Mazal P, Mestre-Alagarda C, Del Burgo PM, van Dijkum EJMN, Oleinikov K, Orci LA, Panzuto F, Pavel M, Perrier M, Reims HM, Rindi G, Rinke A, Rinzivillo M, Sagaert X, Satiroglu I, Selberherr A, Siebenhuner AR, Tesselaar MET, Thalhammer MJ, Thiis-Evensen E, Toumpanakis C, Vandamme T, van den Berg JG, Vanoli A, van Velthuysen MF, Verslype C, Vorburger SA, Lugli A, Ramage J, Zwahlen M, Perren A, Kaderli RM. Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study. Lancet Oncol. 2023 Feb;24(2):187-194. doi: 10.1016/S1470-2045(22)00750-1. Epub 2023 Jan 11. — View Citation

Partelli S, Massironi S, Zerbi A, Niccoli P, Kwon W, Landoni L, Panzuto F, Tomazic A, Bongiovanni A, Kaltsas G, Sauvanet A, Bertani E, Mazzaferro V, Caplin M, Armstrong T, Weickert MO, Ramage J, Segelov E, Butturini G, Staettner S, Cives M, Frilling A, Moulton CA, He J, Boesch F, Selberheer A, Twito O, Castaldi A, De Angelis CG, Gaujoux S, Holzer K, Wilson CH, Almeamar H, Vigia E, Muffatti F, Luca M, Lania A, Ewald J, Kim H, Salvia R, Rinzivillo M, Smid A, Gardini A, Tsoli M, Hentic O, Colombo S, Citterio D, Toumpanakis C, Ramsey E, Randeva HS, Srirajaskanthan R, Croagh D, Regi P, Gasteiger S, Invernizzi P, Ridolfi C, Giovannini M, Jang JY, Bassi C, Falconi M. Management of asymptomatic sporadic non-functioning pancreatic neuroendocrine neoplasms no larger than 2 cm: interim analysis of prospective ASPEN trial. Br J Surg. 2022 Nov 22;109(12):1186-1190. doi: 10.1093/bjs/znac267. No abstract available. — View Citation

Partelli S, Mazza M, Andreasi V, Muffatti F, Crippa S, Tamburrino D, Falconi M. Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: Limitations to apply guidelines into real life. Surgery. 2019 Aug;166(2):157-163. doi: 10.1016/j.surg.2019.04.003. Epub 2019 May 17. — View Citation

Pea A, Tanno L, Nykanen T, Prasad P, Tuncer C, Robinson S, Marchegiani G. Comparison of Oncological and Surgical Outcomes Between Formal Pancreatic Resections and Parenchyma-Sparing Resections for Small PanNETs (<2 cm): Pancreas2000 Research and Educational Program (Course 9) Study Protocol. Front Med (Lausanne). 2020 Sep 10;7:559. doi: 10.3389/fmed.2020.00559. eCollection 2020. — View Citation

Tanaka M, Heckler M, Mihaljevic AL, Probst P, Klaiber U, Heger U, Schimmack S, Buchler MW, Hackert T. Systematic Review and Metaanalysis of Lymph Node Metastases of Resected Pancreatic Neuroendocrine Tumors. Ann Surg Oncol. 2021 Mar;28(3):1614-1624. doi: 10.1245/s10434-020-08850-7. Epub 2020 Jul 27. — View Citation

Tsuchikawa T, Tanaka K, Nakanishi Y, Asano T, Noji T, Nakamura T, Okamura K, Shichinohe T, Hirano S. Clinical Impact of Organ-Preserving Surgery for Pancreatic Neuroendocrine Neoplasms: A Single-Center Experience. Pancreas. 2021 Feb 1;50(2):196-200. doi: 10.1097/MPA.0000000000001739. — View Citation

Xu JZ, Wang WQ, Zhang SR, Xu HX, Wu CT, Qi ZH, Gao HL, Ni QX, Liu L, Yu XJ. Intrinsic Contact Between T and N Classifications in Resected Well-Moderately Differentiated Locoregional Pancreatic Neuroendocrine Neoplasms. Ann Surg Oncol. 2018 Mar;25(3):647-654. doi: 10.1245/s10434-017-6289-1. Epub 2017 Dec 12. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	The time from the surgery to death from any cause.	Through study completion, an average of 1 year.
Primary	Disease-free survival (DFS)	The time of surgery to the time of tumor recurrence or death from any cause.	Through study completion, an average of 1 year.
Secondary	Perioperative complication rate	Adverse events that occur during or after the surgery, including the incidence of postoperative complications reported according to the Clavien-Dindo classification, clinical relevant postoperative pancreatic fistula (POPF), postoperative pancreatic hemorrhage (PPH), delayed gastric emptying (DGE), reoperation rate and mortality rate within 90 days after surgery.	Within 90 days after surgery.
Secondary	Postoperative pathological staging	The tumor staging according to the 8th edition of the AJCC TNM staging system.	From the date of surgery to 1 month after surgery.
Secondary	G staging	The G staging evaluated according to the 2019 WHO classification and grading criteria for digestive neuroendocrine tumors.	From the date of surgery to 1 month after surgery.
Secondary	R0 resection rate	R0 margin rate on postoperative pathological assessment.	From the date of surgery to 1 month after surgery.
Secondary	Lymph node positivity rate	Lymph node positivity rate on postoperative pathological assessment.	From the date of surgery to 1 month after surgery.
Secondary	Life quality satisfaction evaluated according to a scale.	The patient's health-related quality of life after surgical intervention. It includes physical, emotional, and social aspects of a patient's well-being. This study evaluated quality of life using a telephone survey.	Through study completion, an average of 1 year.