ORIGINAL ARTICLE Outcome of peptide receptor radionuclide therapy with 177 Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours Samer Ezziddin & Feras Khalaf & Maria Vanezi & Torjan Haslerud & Karin Mayer & Abdullah Al Zreiqat & Winfried Willinek & Hans-Jürgen Biersack & Amir Sabet Received: 13 August 2013 /Accepted: 20 December 2013 # Springer-Verlag Berlin Heidelberg 2014 Abstract Purpose The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with 177 Lu- octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). Methods We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with 177 Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modi- fied Southwest Oncology Group (SWOG) criteria and addition- ally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate anal- yses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial 99m Tc-DTPA clearance measurements. Results The median follow-up period was 58 months (range 4 – 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and pro- gressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 – 42) and 53 months (95 % CI 46 – 60), respectively. A G1 proliferation status was associated with longer PFS ( p =0.04) and OS (p = 0.044) in the multivariate analysis. Variables linked to impaired OS, on the other hand, were a reduced performance status (Karnofsky score ≤70 %, p =0.007), a high hepatic tumour burden (≥25 % liver volume, p =0.017), and an elevated plasma level of neuron-specific enolase (NSE >15 ng/ml, p =0.035). Conclusion The outstanding response rates and survival outcomes suggest that PRRT is highly effective in ad- vanced G1/2 pNET when compared to data of other treatment modalities. Independent predictors of survival are the tumour proliferation index, the patient’ s perfor- mance status, tumour burden and baseline plasma NSE level. Keywords PRRT . 177 Lu-octreotate . Pancreatic NET . Neuroendocrine tumours . Radionuclide therapy Introduction Increasing evidence supports the efficacy of peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues for metastatic gastroenteropancreatic neuroendo- crine tumours (GEP-NET) [1–3]. However, due to the S. Ezziddin (*) : F. Khalaf : M. Vanezi : T. Haslerud : A. Al Zreiqat : H.<J. Biersack : A. Sabet Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany e-mail: samer.ezziddin@ukb.uni-bonn.de K. Mayer Department of Internal Medicine and Oncology, University Hospital, Bonn, Germany W. Willinek Department of Radiology, University Hospital, Bonn, Germany Eur J Nucl Med Mol Imaging DOI 10.1007/s00259-013-2677-3