Neuroendocrine Tumors of the Pancreas: What's New

  • Anastasios T Dimou Yale Pathology Department, Yale University School of Medicine. New Haven, CT, USA
  • Konstantinos N Syrigos Yale Cancer Center, Yale University School of Medicine. New Haven, CT, USA
  • Muhammad Wasif Saif Yale Cancer Center, Yale University School of Medicine. New Haven, CT, USA
Keywords: Chemoembolization, Therapeutic, everolimus, Ki-67 Antigen, mTOR protein, Neuroendocrine Tumors, sunitinib

Abstract

Surgical excision has been the mainstay of treatment for neuroendocrine tumors of the pancreas (PNET). Compounds like streptozocin and dacarbazin have been traditionally used in inoperable cases and somatostatin to treat syndromes deriving from functional tumors. However, a lot of progress has taken place in the area of molecular characterization of these tumors, revealing activation of mammalian target of rapamycin (mTOR) and VEGF pathways. Recent data from the 2010 ASCO Gastrointestinal Cancers Symposium demonstrate antitumor activity of everolimus, an mTOR inhibitor in combination with temozolomide in a phase I/II trial and of sunitinib versus placebo in a randomized double blinded phase III trial. The role of modern biologic compounds in the treatment of PNET is not clear yet. In addition, combination of resection and transarterial chemoembolization (TACE) has been proven effective over either modality alone in the treatment of PNET metastatic to the liver in a retrospective analysis. This comes to address the problem of selecting local intervention in a metastatic disease, which has been a reasonable choice for this group of tumors in the past. Last but not least the role of Ki-67 in decision-making in PNET is being discussed.

Image: Yale University School of Medicine. New Haven, CT, USA.

Downloads

Download data is not yet available.

References

Ehehalt F, Saeger HD, Schmidt CM, Grützmann R. Neuroendocrine tumors of the pancreas. Oncologist 2009;14:456-67. [PMID 19411317] (FULL TEXT: http://theoncologist.alphamedpress.org/cgi/content/full/14/5/456)

Franko J, Feng W, Yip L, Genovese E, Moser AJ. Non-functional neuroendocrine carcinoma of the P pancreas: incidence, tumor biology, and outcomes in 2,158 patients. J Gastrointest Surg 2010; 14:541-8. [PMID 19997980] (FULL TEXT: http://www.springerlink.com/content/5717k16827k67658/fulltext.html)

Halfdanarson TR, Rabe KG, Rubin J, Petersen GM. Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol 2008; 19:1727-33. [PMID 18515795] (FULL TEXT: http://annonc.oxfordjournals.org/cgi/content/full/19/10/1727)

Liu DM, Kennedy A, Turner D, Rose SC, Kee ST, Whiting S, et al. Minimally invasive techniques in management of hepatic neuroendocrine metastatic disease. Am J Clin Oncol 2009; 32:200-15. [PMID 19346815] (FULL TEXT: http://journals.lww.com/amjclinicaloncology/Citation/2009/04000/Minimally_Invasive_Techniques_in_Management_of.18.aspx)

Hill JS, McPhee JT, McDade TP, Zhou Z, Sullivan ME, Whalen GF, Tseng JF. Pancreatic neuroendocrine tumors: the impact of surgical resection on survival. Cancer 2009; 115:741-51. [PMID 19130464] (FULL TEXT: http://www3.interscience.wiley.com/cgi-bin/fulltext/121622438/HTMLSTART)

Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 1992; 326:519-23. [PMID 1310159]

Kouvaraki MA, Ajani JA, Hoff P, Wolff R, Evans DB, Lozano R, Yao JC. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol 2004; 22:4762-71. [PMID 15570077] (FULL TEXT: http://jco.ascopubs.org/cgi/content/full/22/23/4762)

Ramanathan RK, Cnaan A, Hahn RG, Carbone PP, Haller DG. Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Ann Oncol 2001; 12:1139-43. [PMID 11583197] (FULL TEXT: http://annonc.oxfordjournals.org/cgi/reprint/12/8/1139)

Arnold R, Müller H, Schade-Brittinger C, Rinke A, Klose K, Barth P, et al. Placebo-controlled, double-blind, prospective, randomized study of 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. ASCO Annual Meeting 2009:Abstracts 4508. ] (FULL TEXT: http://meeting.ascopubs.org/cgi/content/abstract/27/15S/4508)

Raymond E, Niccoli-Sire P, Bang Y, Borbath I, Lombard-Bohas C,Valle JW, et al. Updated results of the phase III trial of sunitinib (SU) versus placebo (PBO) for treatment of advanced pancreatic neuroendocrine tumors (NET). 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No. 127. ] (FULL TEXT: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=72&abstractID=1797)

Kulke M, Blaszkowsky LS, Zhu AX, Florio S, Regan E, Ryan DP, Chan JA. Phase I/II study of everolimus (RAD001) in combination with temozolomide (TMZ) in patients (pts) with advanced pancreatic neuroendocrine tumors (NET). 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No. 223. ] (FULL TEXT: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=72&abstractID=2350)

Celinski SA, Nguyen KT, Steel JL, Mehra R, Marsh JW, Geller DA, et al. Multimodality management of neuroendocrine tumors metastatic to the liver. 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No. 234. ] (FULL TEXT: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=72&abstractID=2352)

Singh S, Rowsell C, IngbeN, Law C. The role of Ki-67 in the prognosis and management of neuroendocrine (NET) patients in a multidisciplinary cancer center. 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No. 266. ] (FULL TEXT: http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=72&abstractID=2300)

Missiaglia E, Dalai I, Barbi S, Beghelli S, Falconi M, della Peruta M, et al. Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway. J Clin Oncol 2010; 28:245-55. [PMID 19917848] (FULL TEXT: http://jco.ascopubs.org/cgi/content/full/28/2/245)

Grozinsky-Glasberg S, Franchi G, Teng M, Leontiou CA, Ribeiro de Oliveira A Jr, Dalino P, et al. Octreotide and the mTOR inhibitor RAD001 (everolimus) block proliferation and interact with the Akt-mTOR-p70S6K pathway in a neuro-endocrine tumour cell Line. Neuroendocrinology 2008; 87:168-81. [PMID 18025810] (FULL TEXT: http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000111501)

Zitzmann K, De Toni EN, Brand S, Göke B, Meinecke J, Spöttl G, Meyer HH, Auernhammer CJ. The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells. Neuroendocrinology 2007; 85:54-60. [PMID 17310129] (FULL TEXT: http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000100057)

Moreno A, Akcakanat A, Munsell MF, Soni A, Yao JC, Meric-Bernstam F. Antitumor activity of rapamycin and octreotide as single agents or in combination in neuroendocrine tumors. Endocr Relat Cancer 2008; 15:257-66. [PMID 18310292] (FULL TEXT: http://erc.endocrinology-journals.org/cgi/content/full/15/1/257)

Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, et al. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol 2008; 26:4311-8. [PMID 18779618] (FULL TEXT: http://jco.ascopubs.org/cgi/content/full/26/26/4311)

Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, et al. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 2010; 28:69-76. [PMID 19933912] (FULL TEXT: http://jco.ascopubs.org/cgi/content/full/28/1/69)

Kulke MH, Stuart K, Enzinger PC, Ryan DP, Clark JEW, Muzikansky A, et al. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol 2006; 24:401-6. [PMID 16421420] (FULL TEXT: http://jco.ascopubs.org/cgi/content/full/24/3/401)

La Rosa S, Uccella S, Finzi G, Albarello L, Sessa F, Capella C. Localization of vascular endothelial growth factor and its receptors in digestive endocrine tumors: correlation with microvessel density and clinicopathologic features. Hum Pathol 2003; 34:18-27. [PMID 12605362] (FULL TEXT: http://www.humanpathol.com/article/PIIS004681770300011X/fulltext)

Terris B, Scoazec JY, Rubbia L, Bregeaud L, Pepper MS, Ruszniewski P, et al. Expression of vascular endothelial growth factor in digestive neuroendocrine tumours. Histopathology 1998; 32:133-8. [PMID 9543669] (FULL TEXT: http://www3.interscience.wiley.com/cgi-bin/fulltext/119122740/HTMLSTART)

Kulke MH, Lenz HJ, Meropol NJ, Posey J, Ryan DP, Picus J, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol 2008; 26:3403-10. [PMID 18612155] (FULL TEXT: http://jco.ascopubs.org/cgi/content/full/26/20/3403)

Yale University School of Medicine. New Haven, CT, USA
Published
2010-03-05
How to Cite
DimouA., SyrigosK., & SaifM. (2010). Neuroendocrine Tumors of the Pancreas: What’s New. JOP. Journal of the Pancreas, 11(2), 135-138. https://doi.org/10.6092/1590-8577/3846
Section
Highlights from the “2010 ASCO Gastrointestinal Cancers Symposium”. Orlando, FL, USA. January 22-24, 2010

Most read articles by the same author(s)