Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index

Silvia Nicolini, Stefano Severi, Annarita Ianniello, Maddalena Sansovini, Alice Ambrosetti, Alberto Bongiovanni, Emanuela Scarpi, Francesca Di Mauro, Alice Rossi, Federica Matteucci, Giovanni Paganelli

Research output: Contribution to journalArticle


Purpose: In the 2010 WHO classification, a Ki-67 proliferation index of 20% is the cut-off between intermediate-grade and high-grade gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN). However, in clinical practice, tumours with a Ki-67 index of >15% are often considered high grade and treated with chemotherapy. In 40–70% of high-grade NENs, somatostatin receptors are overexpressed, enabling peptide receptor radionuclide therapy (PRRT) to be performed. We investigated the role of PRRT with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index. Methods: A total of 33 patients with advanced GEP-NENs, positive somatostatin receptor imaging (SRI+) and a Ki-67 proliferation index ranging from 15% to 70% were treated with Lu-PRRT. A cumulative activity of 18.5 GBq or 27.8 GBq of 177Lu-DOTATATE was administered in four or five cycles. Receiver operating characteristic (ROC) curve analysis was used to determine the best threshold of Ki-67 expression to predict disease progression. Results: All patients completed the intended treatment. The median follow-up was 43 months (range 3–69 months). Two patients (6%) achieved a partial response and 21 (64%) showed stable disease, giving a disease control rate (DCR) of 70%. The median progression-free survival (PFS) was 23 months (95% CI 14.9–31.0 months) and the median overall survival was 52.9 months (95% CI 17.1–68.9 months). ROC curve analysis at 23 months revealed that the best Ki-67 index cut-off was 35%. In 23 patients (70%) the Ki-67 index was ≤35% and in 10 patients (30%) the Ki-67 index was in the range 36–70%. The DCR in the former group was 87% and 30% in the latter. The median PFS was 26.3 months (95% CI 18.4–37.7 months) and 6.8 months (95% CI 2.1–27 months), respectively (p = 0.005). Conclusions: Lu-PRRT showed antitumour activity in SRI+ GEP-NENs of intermediate and high-grade. DCR and PFS were significantly better in patients with a Ki-67 index of ≤35% than in those with a Ki-67 index of >35%. On the basis of these results, PRRT should be considered as a therapeutic option in patients with high-grade SRI+ GEP-NENs, in particular those with a Ki-67 proliferation index of ≤35%.

Original languageEnglish
Pages (from-to)923-930
Number of pages8
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Issue number6
Publication statusPublished - Jun 1 2018



  • Ki-67
  • Neuroendocrine tumours
  • PRRT
  • WHO classification

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this