Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN) - a single-institution retrospective analysis

  • Sue Ping Thang
  • Mei Sim Lung
  • Grace Kong
  • Michael S. Hofman
  • Jason Callahan
  • Michael Michael
  • Rodney J. HicksEmail author
Original Article



Grade 3 NENs are aggressive tumours with poor prognosis. PRRT+/− radiosensitising chemotherapy is a potential treatment for disease with high somatostatin receptor (SSTR) expression without spatially discordant FDG-avid disease. We retrospectively evaluated the efficacy of PRRT in G3 NEN.


Kaplan–Meier estimation was used to determine progression-free survival (PFS) and overall survival (OS) defined from start of PRRT. Subgroup analysis was performed for patients with Ki-67 ≤ 55% and >55%. Anatomical response (RECIST 1.1) and toxicity 3 months after PRRT was determined. Disease control rate (DCR) was defined as complete response (CR), partial response (PR) and stable disease (SD) of those with prior progression.


28 patients (M = 17; age 16–78 years; Ki-67 ≤ 55% = 22) were reviewed. 17 patients had pancreatic, 5 small bowel, 3 large bowel, 2 bronchial and 1 unknown primary disease. 25/28 had significant FDG-avid disease prior to treatment. Most had 177Lu-DOTA-octreotate (median cumulative activity 24.4 GBq, median 4 cycles). Twenty patients had radiosensitising chemotherapy. 89% were treated for disease progression; 79% after prior chemotherapy. Median follow-up was 29 months. The median PFS was 9 months for all patients. 16 patients died (Ki-67 ≤ 55% = 11; Ki-67 > 55% = 5) with median OS of 19 months. For Ki-67 ≤ 55% (N = 22), the median PFS was 12 months and median OS 46 months. For Ki-67 > 55% (N = 6), the median PFS was 4 months and median OS 7 months. On CT imaging, DCR at 3 months post-PRRT was 74%, 35% (8/23) PR and 39% (9/23) SD. Eleven patients received further PRRT due to recrudescent disease after response. Five patients developed progression of discordant FDG-avid disease and were referred for targeted therapy/chemotherapy. Grade 3 and 4 lymphopenia and thrombocytopenia occurred in five and five patients, respectively. No renal or liver toxicity related to treatment was seen.


PRRT achieves clinically relevant disease control with acceptable toxicity in G3 NENs.


Lutetium Neuroendocrine Octreotate Peptide receptors Radionuclide therapy G3 



Professor Hicks’ research is supported by a National Health and Medical Research Council of Australia Program grant and practitioner fellowship. We thank our radiopharmacists and radiochemists for their excellent support of our theranostics program and our dedicated nuclear medicine technologists and nursing staff for the care of our patients. Finally, we are grateful for the trust invested in us by our patients, their families and their managing clinicians.

Compliance with ethical standards

Conflict of interest

All authors declare no conflicts of interest. No funding was received. All procedures performed were in accordance with the ethical standards of the institutional research committee and all patients provided informed consent for treatment.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Sue Ping Thang
    • 1
    • 3
  • Mei Sim Lung
    • 2
  • Grace Kong
    • 1
  • Michael S. Hofman
    • 1
  • Jason Callahan
    • 1
  • Michael Michael
    • 2
  • Rodney J. Hicks
    • 1
    Email author
  1. 1.Centre for Cancer ImagingPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Division of Cancer Medicine, Neuroendocrine Tumour UnitPeter MacCallum Cancer CentreMelbourneAustralia
  3. 3.Department of Nuclear Medicine and PETSingapore General HospitalSingaporeSingapore

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