Abstract
Purpose
The role of the Ki-67 tumour proliferation index (PI) in predicting the efficacy of peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic tumours (GEP-NET) remains undetermined. This single-centre analysis focused on the potential therapeutic impact of this immunohistochemical parameter.
Methods
A total of 81 consecutive GEP-NET patients treated with 177Lu-DOTA-octreotate (mean activity of 7.9 GBq per cycle, usually four treatment cycles at standard intervals of 3 months) were retrospectively analysed. Both an evaluable PI and tumour response (modified SWOG criteria) were required for patient inclusion.
Results
Response of tumours with a PI of ≤20% (partial response 40%, minor response 15%, stable disease 34%, progressive disease 11%) was comparable in all PI subsets, including those with a PI of 20%. However, G3 tumours (PI > 20%) showed progression in 71% of patients.
Conclusion
Response to PRRT is consistent over the PI range of ≤20% (G1 + G2). Contrary to preliminary previous suggestions, a PI of 15% or 20% should not preclude candidates from somatostatin receptor-targeted radiotherapy.
This is a preview of subscription content, log in via an institution to check access.
References
van Essen M, Krenning EP, de Jong M, Valkema R, Kwekkeboom DJ. Peptide receptor radionuclide therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours. Acta Oncol 2007;46:723–34.
Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124–30.
Rindi G, Klöppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2006;449:395–401.
Rindi G, Klöppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007;451:757–62.
Pape U, Jann H, Müller-Nordhorn J, et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 2008;113:256–65.
Strosberg J, Nasir A, Coppola D, Wick M, Kvols L. Correlation between grade and prognosis in metastatic gastroenteropancreatic neuroendocrine tumors. Hum Pathol 2009;40:1262–8.
Vilar E, Salazar R, Pérez-García J, Cortes J, Oberg K, Tabernero J. Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors. Endocr Relat Cancer 2007;14:221–32.
Scheidhauer K, Miederer M, Gaertner FC. PET-CT for neuroendocrine tumors and nuclear medicine therapy options (in German). Radiologe. 2009;49:217–23.
Knapp WH, Arnold R. Consensus protocol of the German Society of Nuclear Medicine and the section NET of the German Society of Endocrinology; workshop peptide receptor radionuclide therapy. Updated 2 December 2008. http://www.net-register.org/wDeutsch/ne_tumore/therapiemoeglichkeiten/peptid_radiorezeptor_therapie.php.
Kwekkeboom DJ, Krenning EP, Lebtahi R, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: peptide receptor radionuclide therapy with radiolabeled somatostatin analogs. Neuroendocrinology 2009;90(2):220–6.
Solcia E, Klöppel G, Sobin LH, et al. Histological typing of endocrine tumours: WHO International Histological Classification of Tumours. 2nd ed. Berlin: Springer; 2000.
Rindi G, D'Adda T, Froio E, Fellegara G, Bordi C. Prognostic factors in gastrointestinal endocrine tumors. Endocr Pathol 2007;18:145–9.
Breeman WA, de Jong M, Visser TJ, Erion JL, Krenning EP. Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur J Nucl Med Mol Imaging 2003;30:917–20.
Breeman WAP, van der Wansem K, Bernard BF, et al. The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity. Eur J Nucl Med Mol Imaging 2003;30:312–5.
Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 1992;10:239–53.
Pape U, Berndt U, Müller-Nordhorn J, et al. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr Relat Cancer 2008;15:1083–97.
Ezziddin S, Logvinski T, Yong-Hing C, et al. Factors predicting tracer uptake in somatostatin receptor and MIBG scintigraphy of metastatic gastroenteropancreatic neuroendocrine tumors. J Nucl Med 2006;47:223–33.
Kayani I, Bomanji JB, Groves A, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG. Cancer 2008;112:2447–55.
Acknowledgments
The authors express their gratitude to Professor Eric Krenning and Professor Dik Kwekkeboom (Erasmus Medical Center, Rotterdam) for generously sharing their invaluable experience and pioneering work as well as the supply of peptides. We also thank Tobias Höller (Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn) for his excellent statistical support and advice.
Author information
Authors and Affiliations
Corresponding author
Additional information
Samer Ezziddin and Martin Opitz contributed equally to this work.
Rights and permissions
About this article
Cite this article
Ezziddin, S., Opitz, M., Attassi, M. et al. Impact of the Ki-67 proliferation index on response to peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 38, 459–466 (2011). https://doi.org/10.1007/s00259-010-1610-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-010-1610-2