title: Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours.
abstract: OBJECTIVE
  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 modified Southwest Oncology Group (SWOG) criteria and additionally 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 analyses. 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 progressive 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).
  
  
  CONCLUSIONS
  The outstanding response rates and survival outcomes suggest that PRRT is highly effective in advanced G1/2 pNET when compared to data of other treatment modalities. Independent predictors of survival are the tumour proliferation index, the patient's performance status, tumour burden and baseline plasma NSE level.
authors: Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany, samer.ezziddin@ukb.uni-bonn.de.
authors: Samer
authors: S
authors: Ezziddin
authors: Feras
authors: F
authors: Khalaf
authors: Maria
authors: M
authors: Vanezi
authors: Torjan
authors: T
authors: Haslerud
authors: Karin
authors: K
authors: Mayer
authors: Abdullah
authors: A
authors: Al Zreiqat
authors: Winfried
authors: W
authors: Willinek
authors: Hans-Jürgen
authors: HJ
authors: Biersack
authors: Amir
authors: A
authors: Sabet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: C554548:177Lu-octreotate; D019275:Radiopharmaceuticals; D015282:Octreotide