Abstract
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 language | English |
|---|---|
| Pages (from-to) | 923-930 |
| Number of pages | 8 |
| Journal | European Journal of Nuclear Medicine and Molecular Imaging |
| Volume | 45 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2018 |
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Keywords
- Lu-DOTATATE
- GEP-NEC
- GEP-NEN
- Ki-67
- Neuroendocrine tumours
- PRRT
- WHO classification
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
Cite this
Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index. / Nicolini, Silvia; Severi, Stefano; Ianniello, Annarita; Sansovini, Maddalena; Ambrosetti, Alice; Bongiovanni, Alberto; Scarpi, Emanuela; Di Mauro, Francesca; Rossi, Alice; Matteucci, Federica; Paganelli, Giovanni.
In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 45, No. 6, 01.06.2018, p. 923-930.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Investigation of receptor radionuclide therapy with 177Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index
AU - Nicolini, Silvia
AU - Severi, Stefano
AU - Ianniello, Annarita
AU - Sansovini, Maddalena
AU - Ambrosetti, Alice
AU - Bongiovanni, Alberto
AU - Scarpi, Emanuela
AU - Di Mauro, Francesca
AU - Rossi, Alice
AU - Matteucci, Federica
AU - Paganelli, Giovanni
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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%.
AB - 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%.
KW - Lu-DOTATATE
KW - GEP-NEC
KW - GEP-NEN
KW - Ki-67
KW - Neuroendocrine tumours
KW - PRRT
KW - WHO classification
UR - http://www.scopus.com/inward/record.url?scp=85044922561&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044922561&partnerID=8YFLogxK
U2 - 10.1007/s00259-017-3925-8
DO - 10.1007/s00259-017-3925-8
M3 - Article
C2 - 29387927
AN - SCOPUS:85044922561
VL - 45
SP - 923
EP - 930
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
SN - 0340-6199
IS - 6
ER -