Skip to main content
Log in

Imaging response in neuroendocrine tumors treated with targeted therapies: the experience of sunitinib

  • Review
  • Published:
Targeted Oncology Aims and scope Submit manuscript

Abstract

Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly vascularized, featuring specific characteristics on contrast-enhanced imaging. Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular enhancement, coexisting with areas of necrosis mainly located at the center of tumor lesions. When exposed to vascular endothelial growth factor (VEGFR) inhibitors such as sunitinib, target lesions display few if any variation in tumor size, but rather detectable modifications in tumor density. In several patients treated with targeted therapy, a significant decrease of tumor density at first tumor evaluation can be detected as compared to baseline. Consistently, the two randomized trials leading to approval of sunitinib and everolimus in pancreatic neuroendocrine tumors report objective response rate below 10 %, emphasizing that Response Evaluation Criteria in Solid Tumors (RECIST), that focus only on the largest diameters of target lesions, may be insufficient to capture the full benefit of targeted therapies. Alternative criteria, such as those developed by Choi et al., consider both the size and the density of the tumor as parameters for response evaluation. Choi criteria have been recently proposed as a surrogate endpoint for efficacy and to identify patients that are good responders to VEGFR inhibitors such as sunitinib and sorafenib in advanced hepatocellular carcinoma, another disease highly addicted to angiogenesis. Preliminary data generated from patients included in the sunitinib phase III trial suggest that Choi criteria might also be considered as an alternative to RECIST to evaluate the effects of sunitinib in patients with advanced well-differentiated neuroendocrine tumors.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Joensuu H, Roberts PJ, Sarlomo-Rikala M et al (2001) Effect of the tyrosine kinase inhibitor STI-571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052–1056

    Article  PubMed  CAS  Google Scholar 

  2. 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  PubMed  CAS  Google Scholar 

  3. 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  PubMed  CAS  Google Scholar 

  4. Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124

    Article  PubMed  CAS  Google Scholar 

  5. Verweij J, Casali PG, Zalcberg J et al (2004) Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 364:1127–1134

    Article  PubMed  CAS  Google Scholar 

  6. Blanke CD, Rankin C, Demetri GD et al (2008) Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 26:626–632

    Article  PubMed  CAS  Google Scholar 

  7. 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  PubMed  CAS  Google Scholar 

  8. 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 

  9. 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 

  10. 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 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. Couvelard A et al (2005) Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression. Br J Cancer 92:94–101

    Article  PubMed  CAS  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  PubMed  CAS  Google Scholar 

  15. 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 

  16. 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  PubMed  CAS  Google Scholar 

  17. 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  PubMed  CAS  Google Scholar 

  18. 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  PubMed  CAS  Google Scholar 

  19. 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  PubMed  CAS  Google Scholar 

  20. 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  PubMed  CAS  Google Scholar 

  21. 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  PubMed  CAS  Google Scholar 

  22. 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  PubMed  CAS  Google Scholar 

  23. 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  PubMed  CAS  Google Scholar 

  24. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430

    Article  PubMed  CAS  Google Scholar 

  25. Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60

    Article  PubMed  CAS  Google Scholar 

  26. Wassermann J, Bouattour M, Bruno O, Serrate C, Larroque B, Castera L, Dreyer C, Sablin MP, Colichi C, Vilgrain V, Belghiti J, Raymond E, Faivre S (2011) Blinded independent central response assessment using RECIST, mRECIST, and Choi criteria in patients treated with sorafenib for advanced hepatocellular carcinoma (HCC). Proc ILCA Meeting

Download references

Conflicts of interest

All authors of this manuscript have no conflicts of interest except for Sandrine Faivre and Eric Raymond who were compensated with honorarium from Pfizer and Novartis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sandrine Faivre.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faivre, S., Ronot, M., Dreyer, C. et al. Imaging response in neuroendocrine tumors treated with targeted therapies: the experience of sunitinib. Targ Oncol 7, 127–133 (2012). https://doi.org/10.1007/s11523-012-0216-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-012-0216-y

Keywords

Navigation