Skip to main content
SpringerLink
Log in

Imaging of Neuroendocrine Tumors and Challenges in Response Evaluation for Targeted Therapies

  • Chapter
  • First Online:
Management of Neuroendocrine Tumors of the Pancreas and Digestive Tract

  • 1279 Accesses

Abstract

Targeted therapies such as sunitinib and everolimus have emerged as novel treatment options for patients with pancreatic neuroendocrine tumors (PNET). Clinical trials are also pending for non-pancreatic neuroendocrine tumors. Large randomized trials using sunitinib and everolimus in PNET demonstrated that response rate by Response Evaluation Criteria in Solid Tumors (RECIST) was insufficient to predict the overall patients’ outcome and did not correlate with progression-free survival. Using RECIST, most patients receiving targeted agents have experienced tumor stabilization. Disappointedly, tumor stabilization by RECIST made impossible to recognize during the course of therapy the subset of patients who were truly benefiting from treatments. Therefore, investigators have started to seek for other imaging methods and criteria that could help identifying true responders from patients receiving targeted agents. In this chapter, we aimed to review the various imaging techniques used to characterize neuroendocrine tumors in routine clinic and clinical trials. We also challenge the potential advantages of those imaging techniques for the evaluation of response in patients with neuroendocrine tumors. Finally, we discuss novel criteria that are not only based on measurement of tumor dimension but also rely on tumor density such as Choi criteria.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Raymond E et al (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364:501–513

    Article  CAS  PubMed  Google Scholar 

  2. Yao JC et al (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364:514–523

    Article  CAS  PubMed  Google Scholar 

  3. Benjamin RS, Choi H, Macapinlac HA, Burgess MA, Patel SR, Chen LL et al (2007) We should desist using RECIST, at least in GIST. J Clin Oncol 25:1760–1764

    Article  PubMed  Google Scholar 

  4. Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR et al (2007) Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 25:1753–1759

    Article  PubMed  Google Scholar 

  5. Faivre S, Zappa M, Vilgrain V, Boucher E, Douillard JY, Lim HY, Kim JS, Im SA, Kang YK, Bouattour M, Dokmak S, Dreyer C, Sablin MP, Serrate C, Cheng AL, Lanzalone S, Lin X, Lechuga MJ, Raymond E (2011) Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib. Clin Cancer Res 17:4504–4512

    Article  CAS  PubMed  Google Scholar 

  6. Low G, Panu A, Millo N, Leen E (2011) Multimodality imaging of neoplastic and nonneoplastic solid lesions of the pancreas. Radiographics 31(4):993–1015

    Article  PubMed  Google Scholar 

  7. Rösch T, Lightdale CJ, Botet JF et al (1992) Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med 326(26):1721–1726

    Article  PubMed  Google Scholar 

  8. Ruszniewski P, Amouyal P, Amouyal G et al (1995) Localization of gastrinomas by endoscopic ultrasonography in patients with Zollinger-Ellison syndrome. Surgery 117(6):629–635

    Article  CAS  PubMed  Google Scholar 

  9. Thompson NW, Czako PF, Fritts LL et al (1994) Role of endoscopic ultrasonography in the localization of insulinomas and gastrinomas. Surgery 116(6):1131–1138

    CAS  PubMed  Google Scholar 

  10. Noone TC, Hosey J, Firat Z et al (2005) Imaging and localization of islet-cell tumours of the pancreas on CT and MRI. Best Pract Res Clin Endocrinol Metab 19(2):195–211

    Article  PubMed  Google Scholar 

  11. Gouya H, Vignaux O, Augui J et al (2003) CT, endoscopic sonography, and a combined protocol for preoperative evaluation of pancreatic insulinomas. AJR Am J Roentgenol 181(4):987–992

    Article  PubMed  Google Scholar 

  12. Owen NJ, Sohaib SA, Peppercorn PD et al (2001) MRI of pancreatic neuroendocrine tumours. Br J Radiol 74(886):968–973

    CAS  PubMed  Google Scholar 

  13. Thoeni RF, Mueller-Lisse UG, Chan R et al (2000) Detection of small, functional islet cell tumors in the pancreas: selection of MR imaging sequences for optimal sensitivity. Radiology 214(2):483–490

    Article  CAS  PubMed  Google Scholar 

  14. Rodallec M et al (2006) Endocrine pancreatic tumours and helical CT: contrast enhancement is correlated with microvascular density, histoprognostic factors and survival. Pancreatology 6:77–85

    Article  CAS  PubMed  Google Scholar 

  15. Chang S, Choi D, Lee SJ et al (2007) Neuroendocrine neoplasms of the gastrointestinal tract: classification, pathologic basis, and imaging features. Radiographics 27(6):1667–1679

    Article  PubMed  Google Scholar 

  16. Rha SE, Jung SE, Lee KH et al (2007) CT and MR imaging findings of endocrine tumor of the pancreas according to WHO classification. Eur J Radiol 62(3):371–377

    PubMed  Google Scholar 

  17. Wang Y, Miller FH, Chen ZE, et al (2011) Diffusion-weighted MR imaging of solid and cystic lesions of the pancreas. Radiographics 31(3):E47–64. Review. (Erratum in: Radiographics. Sep-Oct;31(5):1496)

    Google Scholar 

  18. Alexander HR, Fraker DL, Norton JA et al (1998) Prospective study of somatostatin receptor scintigraphy and its effect on operative outcome in patients with Zollinger-Ellison syndrome. Ann Surg 228(2):228–238

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Zimmer T, Stölzel U, Bäder M et al (1996) Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localisation of insulinomas and gastrinomas. Gut 39(4):562–568

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Cadiot G, Lebtahi R, Sarda L et al (1996) Preoperative detection of duodenal gastrinomas and peripancreatic lymph nodes by somatostatin receptor scintigraphy. Groupe D’etude Du Syndrome De Zollinger-Ellison. Gastroenterology 111(4):845–854

    Article  CAS  PubMed  Google Scholar 

  21. Eriksson B, Bergström M, Orlefors H et al (2000) Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies. Q J Nucl Med 44(1):68–76

    CAS  PubMed  Google Scholar 

  22. Frilling A, Sotiropoulos GC, Radtke A et al (2010) The impact of 68 Ga-DOTATOC positron emission tomography/computed tomography on the multimodal management of patients with neuroendocrine tumors. Ann Surg 252(5):850–856

    Article  PubMed  Google Scholar 

  23. Becherer A, Szabó M, Karanikas G et al (2004) Imaging of advanced neuroendocrine tumors with (18)F-FDOPA PET. J Nucl Med 45(7):1161–1167

    CAS  PubMed  Google Scholar 

  24. Buchmann I, Henze M, Engelbrecht S et al (2007) Comparison of 68 Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 34(10):1617–1626

    Article  CAS  PubMed  Google Scholar 

  25. Dromain C, de Baere T, Lumbroso J et al (2005) Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol 23:70–78

    Article  PubMed  Google Scholar 

  26. Elias D, Lefevre JH, Duvillard P et al (2010) Hepatic metastases from neuroendocrine tumors with a “thin slice” pathological examination: they are many more than you think. Ann Surg 251(2):307–310

    Article  PubMed  Google Scholar 

  27. D’Assignies G, Fina P, Bruno O, et al (2013) High sensitivity of diffusion-weighted MR imaging for the detection of liver metastases from neuroendocrine tumors: comparison with T2-weighted and dynamic gadolinium-enhanced MR imaging. Radiology 268(2):390--399

    Google Scholar 

  28. Faivre S et al (2006) Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 24:25–35

    Article  CAS  PubMed  Google Scholar 

  29. Faivre S, Demetri G, Sargent W, Raymond E (2007) Molecular basis for sunitinib efficacy and future clinical development. Nat Rev Drug Discov 6:734–745

    Article  CAS  PubMed  Google Scholar 

  30. Faivre SJ, Bouattour M, Dreyer C, Raymond E (2009) Sunitinib in hepatocellular carcinoma: redefining appropriate dosing, schedule, and activity end points. J Clin Oncol 27:e248–e250

    Article  CAS  PubMed  Google Scholar 

  31. Zhu AX, Sahani DV, Duda DG, di Tomaso E, Ancukiewicz M, Catalano OA et al (2009) Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 27:3027–3035

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Desar IM, van Herpen CM, van Laarhoven HW, Barentsz JO, Oyen WJ, van der Graaf WT (2009) Beyond RECIST: molecular and functional imaging techniques for evaluation of response to targeted therapy. Cancer Treat Rev 35:309–321

    Article  CAS  PubMed  Google Scholar 

  33. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  34. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  CAS  PubMed  Google Scholar 

  35. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390

    Article  CAS  PubMed  Google Scholar 

  36. Faivre S, Sablin MP, Dreyer C, Raymond E (2010) Novel anticancer agents in clinical trials for well-differentiated neuroendocrine tumors. Endocrinol Metab Clin N Am 39:811–826

    Article  CAS  Google Scholar 

  37. Faivre S, Raymond E, Boucher E et al (2009) Safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma: an open-label, multicentre, phase II study. Lancet Oncol 10:794–800

    Article  CAS  PubMed  Google Scholar 

  38. Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293–4300

    Article  CAS  PubMed  Google Scholar 

  39. Ronot M, Bouattour M, Wassermann J, Bruno O, Dreyer C, Larroque B, Castera L, Vilgrain V, Belghiti J, Raymond E, Faivre S (2014) Alternative response criteria (Choi, EASL, and modified RECIST) versus RECIST 1.1 in patients with advanced hepatocellular carcinoma treated with sorafenib. The Oncologist (in press)

    Google Scholar 

  40. Dreyer C, Hentic O, Zappa M, Hammel P, Mateescu C, Bouattour M, Faivre S, Ruszniewski P, Raymond E (2012) Response evaluation using RECIST and Choi criteria in patient with well-differentiated neuroendocrine tumors either treated with sunitinib or everolimus. In: Proceedings of ESMO Meeting (1163P)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Beaujon University Hospital, Assistance Publique—Hôpitaux de Paris, 100 Boulevard du Général Leclerc, 92110, Clichy, France

    Maxime Ronot, Magaly Zappa & Valérie Vilgrain

  2. Department of Medical Oncology, Beaujon University Hospital, Assistance Publique—Hôpitaux de Paris, 100 Boulevard du Général Leclerc, 92110, Clichy, France

    Chantal Dreyer, Cristian Mateescu, Eric Raymond & Sandrine Faivre

  3. Department of Gastroenterology and Pancreatology, Beaujon University Hospital, Assistance Publique—Hôpitaux de Paris, 100 Boulevard du Général Leclerc, 92110, Clichy, France

    Olivia Hentic & Pascal Hammel

  4. Department of Pathology, Bichat University Hospital, Paris, France

    Anne Couvelard

Authors
  1. Maxime Ronot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chantal Dreyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olivia Hentic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Magaly Zappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cristian Mateescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anne Couvelard
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pascal Hammel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Valérie Vilgrain
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eric Raymond
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sandrine Faivre
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandrine Faivre .

Editor information

Editors and Affiliations

  1. Medical Oncology, Bichat-Beaujon University Hospitals, Clichy cedex, France

    Eric Raymond

  2. Bichat-Beaujon University Hospitals Medical Oncology, Clichy cedex, France

    Sandrine Faivre

  3. Pancreatology, Bichat-Beaujon University Hospitals Gastroenterology and, Clichy cedex, France

    Philippe Ruszniewski

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag France

About this chapter

Cite this chapter

Ronot, M. et al. (2014). Imaging of Neuroendocrine Tumors and Challenges in Response Evaluation for Targeted Therapies. In: Raymond, E., Faivre, S., Ruszniewski, P. (eds) Management of Neuroendocrine Tumors of the Pancreas and Digestive Tract. Springer, Paris. https://doi.org/10.1007/978-2-8178-0430-9_11

Download citation

  • DOI: https://doi.org/10.1007/978-2-8178-0430-9_11

  • Published:

  • Publisher Name: Springer, Paris

  • Print ISBN: 978-2-8178-0429-3

  • Online ISBN: 978-2-8178-0430-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation