177Lu-DOTATATE plus 166Ho-radioembolization in patients with neuroendocrine tumours; a single center, prospective, interventional, non-comparative,...

Date 29 September 2019
Event ESMO 2019 Congress
Session Proffered Paper – NETs and endocrine tumours
Topics Neuroendocrine Tumours
Radiation Oncology
Endocrine Tumours
Presenter Sander Ebbers
Citation Annals of Oncology (2019) 30 (suppl_5): v564-v573. 10.1093/annonc/mdz256
Authors A.J.A.T. Braat1, R. van Rooij2, R.C.G. Bruijnen2, M.N.G.J.A. Braat2, F. Wessels2, S. Ebbers1, R.S. van Leeuwaarde3, M. van Treijen3, H.W.A.M. de Jong2, M.G.E.H. Lam2
  • 1Radiology And Nuclear Medicine, University Medical Center Utrecht, 3584 CX - Utrecht/NL
  • 2Radiology And Nuclear Medicine, University Medical Center Utrecht, Utrecht/NL
  • 3Department Of Endocrinology, University Medical Center Utrecht, Utrecht/NL



The liver is the most commonly affected organ in metastatic neuroendocrine disease and is the most incriminating factor for patient survival. Additional treatment of liver disease with radioembolization may improve outcome in NET patients with bulky residual liver disease after PRRT. To investigate this hypothesis, a phase II study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization (166Ho-RE) after PRRT with lutetium-177 (177Lu)-DOTATATE.


The HEPAR PLUS study was a single center, prospective, interventional, non-comparative, open label study. Thirty patients with >3 measurable residual liver metastases according to RECIST 1.1 received 166Ho-RE within 20 weeks after the 4th and last cycle of PRRT with 7.4 GBq 177Lu-DOTATATE. Primary objectives: objective response rate (ORR = complete plus partial response) after three months according to RECIST 1.1 (treatment volume, liver and patient-based analysis). Secondary endpoints included toxicity profile according to CTCAE v4.03 and quality of life assessments according to EORTC QLQ-C30 and GI.NET21 questionnaires.


Three months after PRRT plus 166Ho-RE, liver ORR was 43% according to RECIST 1.1. In patient-based analysis, ORR was 40% according to RECIST 1.1, stable disaese in 50% and three patient (10%) experienced progressive disease (due to progressive lesions or development of new lesions outside the treatment volume). CTCAE grade 3-4 toxicities were limited to abdominal pain (10%), nausea (3%) and fatigue (3%). One related serious adverse event occurred in one patient (3%), fatal radiation induced liver disease. Quality of life assessments showed a temporary non-significant decrease in most scales at three weeks post-treatment and complete resolution three months after treatment.


This was the first prospective study to combine PRRT and 166Ho-RE in metastatic NET. A radiation boost on intrahepatic disease using 166Ho-RE leads to a high objective response rate without significant additional short-term side-effects, and a temporary non-significant decrease in quality of life in well-selected patients.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

The authors.


Has not received any funding.


A.J.A.T. Braat: Non-remunerated activity/ies: Terumo; Non-remunerated activity/ies: BTG; Non-remunerated activity/ies: Sirtex Medical. M.G.E.H. Lam: Honoraria (institution), Non-remunerated activity/ies: Terumo; Advisory / Consultancy, Non-remunerated activity/ies: BTG; Advisory / Consultancy, Non-remunerated activity/ies: Sirtex Medical; Non-remunerated activity/ies: Mirada. All other authors have declared no conflicts of interest.