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Baylor University Medical Center Proceedings
The peer-reviewed journal of Baylor Scott & White Health
Volume 37, 2024 - Issue 1
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Resistant gastroenteropancreatic neuroendocrine tumors: a definition and guideline to medical and surgical management

, MD, MPHORCID Icon, , MD & , MD
Pages 104-110 | Received 22 Aug 2023, Accepted 07 Nov 2023, Published online: 20 Dec 2023

  • Pearse AG. The APUD concept and hormone production. Clin Endocrinol Metab. 1980;9(2):211–222. doi:10.1016/s0300-595x(80)80030-2.
  • Zandee WT, Kamp K, van Adrichem RC, Feelders RA, de Herder WW. Effect of hormone secretory syndromes on neuroendocrine tumor prognosis. Endocr Relat Cancer. 2017;24(7):R261–R274. doi:10.1530/ERC-16-0538.
  • Kyriakopoulos G, Mavroeidi V, Chatzellis E, Kaltsas GA, Alexandraki KI. Histopathological, immunohistochemical, genetic and molecular markers of neuroendocrine neoplasms. Ann Transl Med. 2018;6(12):252–252. doi:10.21037/atm.2018.06.27.
  • Niederle MB, Hackl M, Kaserer K, Niederle B. Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. Endocr Relat Cancer. 2010;17(4):909–918. doi:10.1677/ERC-10-0152.
  • Dasari A, Shen C, Halperin D, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3(10):1335–1342. doi:10.1001/jamaoncol.2017.0589.
  • Pavel M, Öberg K, Falconi M, et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(7):844–860. doi:10.1016/j.annonc.2020.03.304.
  • Rindi G, Inzani F. Neuroendocrine neoplasm update: toward universal nomenclature. Endocr Relat Cancer. 2020;27(6):R211–R218. doi:10.1530/ERC-20-0036.
  • Modlin IM, Lye KD, Kidd M. Carcinoid tumors of the stomach. Surg Oncol. 2003;12(2):153–172. doi:10.1016/s0960-7404(03)00034-3.
  • Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135(5):1469–1492. doi:10.1053/j.gastro.2008.05.047.
  • Sundin A, Arnold R, Baudin E, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: radiological, nuclear medicine & hybrid imaging. Neuroendocrinology. 2017;105(3):212–244. doi:10.1159/000471879.
  • Gabriel S, Garrigue P, Dahan L, et al. Prospective evaluation of (68) Ga-DOTATATE PET/CT in limited disease neuroendocrine tumours and/or elevated serum neuroendocrine biomarkers. Clin Endocrinol (Oxf). 2018;89(2):155–163. doi:10.1111/cen.13745.
  • Hope TA, Bergsland EK, Bozkurt MF, et al. Appropriate use criteria for somatostatin receptor PET imaging in neuroendocrine tumors. J Nucl Med. 2018;59(1):66–74. doi:10.2967/jnumed.117.202275.
  • Sadowski SM, Neychev V, Millo C, et al. Prospective study of 68Ga-DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic neuroendocrine tumors and unknown primary sites. J Clin Oncol. 2016;34(6):588–596. doi:10.1200/JCO.2015.64.0987.
  • Ma ZY, Gong YF, Zhuang HK, et al. Pancreatic neuroendocrine tumors: a review of serum biomarkers, staging, and management. World J Gastroenterol. 2020;26(19):2305–2322. doi:10.3748/wjg.v26.i19.2305.
  • Philips P, Kooby DA, Maithel S, et al. Grading using Ki-67 index and mitotic rate increases the prognostic accuracy of pancreatic neuroendocrine tumors. Pancreas. 2018;47(3):326–331. doi:10.1097/MPA.0000000000000990.
  • Howe JR, Merchant NB, Conrad C, et al. The North American Neuroendocrine Tumor Society consensus paper on the surgical management of pancreatic neuroendocrine tumors. Pancreas. 2020;49(1):1–33. doi:10.1097/MPA.0000000000001454.
  • Jung JG, Lee KT, Woo YS, et al. Behavior of small, asymptomatic, nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs). Medicine (Baltimore). 2015;94(26):e983. doi:10.1097/MD.0000000000000983.
  • Sallinen VJ, Le Large TYS, Tieftrunk E, et al. Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors—a multi-institutional study. HPB (Oxford). 2018;20(3):251–259. doi:10.1016/j.hpb.2017.08.034.
  • Triponez F, Sadowski SM, Pattou F, et al. Long-term follow-up of MEN1 patients who do not have initial surgery for small ≤2 cm nonfunctioning pancreatic neuroendocrine tumors, an AFCE and GTE study: Association Francophone de Chirurgie Endocrinienne & Groupe d‘Etude des Tumeurs Endocrines. Ann Surg. 2018;268(1):158–164. doi:10.1097/SLA.0000000000002191.
  • Barenboim A, Lahat G, Nachmany I, et al. Resection versus observation of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors. J Gastrointest Surg. 2020;24(6):1366–1374. doi:10.1007/s11605-019-04285-y.
  • Fernandez CJ, Agarwal M, Pottakkat B, Haroon NN, George AS, Pappachan JM. Gastroenteropancreatic neuroendocrine neoplasms: a clinical snapshot. World J Gastrointest Surg. 2021;13(3):231–255. doi:10.4240/wjgs.v13.i3.231.
  • Kalshetty A, Ramaswamy A, Ostwal V, Basu S. Resistant functioning and/or progressive symptomatic metastatic gastroenteropancreatic neuroendocrine tumors: efficacy of 177Lu-DOTATATE peptide receptor radionuclide therapy in this setting. Nucl Med Commun. 2018;39(12):1143–1149. doi:10.1097/MNM.0000000000000926.
  • Antonuzzo L, Del Re M, Barucca V, et al. Critical focus on mechanisms of resistance and toxicity of m-TOR inhibitors in pancreatic neuroendocrine tumors. Cancer Treat Rev. 2017;57:28–35. doi:10.1016/j.ctrv.2017.05.001.
  • Luley K, Gebauer J, Gebauer N, et al. Gastroenteropancreatic neuroendocrine neoplasms—heterogeneity, management and perspectives of treatment and research. Internist (Berl). 2020;61(8):875–890. doi:10.1007/s00108-020-00832-x.
  • Caplin ME, Pavel M, Ruszniewski P. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(16):1556–1557. doi:10.1056/NEJMc1409757.
  • Modlin IM, Pavel M, Kidd M, Gustafsson BI. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2010;31(2):169–188. doi:10.1111/j.1365-2036.2009.04174.x.
  • Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009;27(28):4656–4663. doi:10.1200/JCO.2009.22.8510.
  • Zanini S, Renzi S, Giovinazzo F, Bermano G. mTOR pathway in gastroenteropancreatic neuroendocrine tumor (carcinoids). Front Endocrinol (Lausanne). 2020;11:562505. doi:10.3389/fendo.2020.562505.
  • Chan DL, Segelov E, Singh S. Everolimus in the management of metastatic neuroendocrine tumours. Therap Adv Gastroenterol. 2017;10(1):132–141. doi:10.1177/1756283X16674660.
  • Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387(10022):968–977. doi:10.1016/S0140-6736(15)00817-X.
  • Pavel ME, Hainsworth JD, Baudin E, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378(9808):2005–2012. doi:10.1016/S0140-6736(11)61742-X.
  • Fazio N, Buzzoni R, Baudin E, et al. A phase II study of BEZ235 in patients with everolimus-resistant, advanced pancreatic neuroendocrine tumours. Anticancer Res. 2016;36(2):713–719.
  • Beyens M, Vandamme T, Peeters M, Van Camp G, Op de Beeck K. Resistance to targeted treatment of gastroenteropancreatic neuroendocrine tumors. Endocr Relat Cancer. 2019;26(3):R109–R130. doi:10.1530/ERC-18-0420.
  • Fazio N, Cella CA, Del Re M, et al. Pharmacodynamics, clinical findings and approval status of current and emerging tyrosine-kinase inhibitors for pancreatic neuroendocrine tumors. Expert Opin Drug Metab Toxicol. 2019;15(12):993–1004. doi:10.1080/17425255.2019.1700951.
  • Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):501–513. doi:10.1056/NEJMoa1003825.
  • Daskalakis K, Tsoli M, Angelousi A, et al. Anti-tumour activity of everolimus and sunitinib in neuroendocrine neoplasms. Endocr Connect. 2019;8(6):641–653. doi:10.1530/EC-19-0134.
  • Hobday TJ, Qin R, Reidy-Lagunes D, et al. Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors. J Clin Oncol. 2015;33(14):1551–1556. doi:10.1200/JCO.2014.56.2082.
  • Tsoli M, Alexandraki K, Xanthopoulos C, Kassi E, Kaltsas G. Medical treatment of gastrointestinal neuroendocrine neoplasms. Horm Metab Res. 2020;52(8):614–620. doi:10.1055/a-1110-7251.
  • Chatzellis E, Angelousi A, Daskalakis K, et al. Activity and safety of standard and prolonged capecitabine/temozolomide administration in patients with advanced neuroendocrine neoplasms. Neuroendocrinology. 2019;109(4):333–345. doi:10.1159/000500135.
  • Brabander T, Teunissen JJ, Van Eijck CH, et al. Peptide receptor radionuclide therapy of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2016;30(1):103–114. doi:10.1016/j.beem.2015.10.005.
  • Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125–135. doi:10.1056/NEJMoa1607427.
  • Brabander T, van der Zwan WA, Teunissen JJM, et al. Long-term efficacy, survival, and safety of [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clin Cancer Res. 2017;23(16):4617–4624. doi:10.1158/1078-0432.CCR-16-2743.
  • Starr JS, Sonbol MB, Hobday TJ, Sharma A, Kendi AT, Halfdanarson TR. Peptide receptor radionuclide therapy for the treatment of pancreatic neuroendocrine tumors: recent insights. Onco Targets Ther. 2020;13:3545–3555. doi:10.2147/OTT.S202867.
  • Sansovini M, Severi S, Ianniello A, et al. Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with. Eur J Nucl Med Mol Imaging. 2017;44(3):490–499. doi:10.1007/s00259-016-3533-z.
  • Cella D, Beaumont JL, Hudgens S, et al. Relationship between symptoms and health-related quality-of-life benefits in patients with carcinoid syndrome: post hoc analyses from TELESTAR. Clin Ther. 2018;40(12):2006–2020.e2. doi:10.1016/j.clinthera.2018.10.008.
  • Falciani C, Brunetti J, Pagliuca C, et al. Design and in vitro evaluation of branched peptide conjugates: turning nonspecific cytotoxic drugs into tumor-selective agents. ChemMedChem. 2010;5(4):567–574. doi:10.1002/cmdc.200900527.
  • Libutti SA, Sosa JA, Kunz P, et al. Phase 2 study of fosbretabulin tromethamine (CA4P) for the treatment of well-differentiated, low-to-intermediate-grade unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors/carcinoid with elevated biomarkers. Abstracts Presented at the 8th Annual Meeting of the North American NeuroEndocrine Tumor Society, October 14–18, 2015, Austin, TX. doi:10.1097/MPA.0000000000000615.
  • Scott AT, Breheny PJ, Keck KJ, et al. Effective cytoreduction can be achieved in patients with numerous neuroendocrine tumor liver metastases (NETLMs). Surgery. 2019;165(1):166–175. doi:10.1016/j.surg.2018.04.070.
  • Morgan RE, Pommier SJ, Pommier RF. Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors. Surgery. 2018;163(1):218–225. doi:10.1016/j.surg.2017.05.030.
  • Maxwell JE, Sherman SK, O’Dorisio TM, Bellizzi AM, Howe JR. Liver-directed surgery of neuroendocrine metastases: what is the optimal strategy? Surgery. 2016;159(1):320–333. doi:10.1016/j.surg.2015.05.040.
  • Que FG, Nagorney DM, Batts KP, Linz LJ, Kvols LK. Hepatic resection for metastatic neuroendocrine carcinomas. Am J Surg. 1995;169(1):36–43. discussion 42-3. doi:10.1016/s0002-9610(99)80107-x.
  • Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg. 2003;197(1):29–37. doi:10.1016/S1072-7515(03)00230-8.
  • De Jong MC, Farnell MB, Sclabas G, et al. Liver-directed therapy for hepatic metastases in patients undergoing pancreaticoduodenectomy: a dual-center analysis. Ann Surg. 2010;252(1):142–148. doi:10.1097/SLA.0b013e3181dbb7a7.

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