title: A systematic review of non-surgical treatments for pancreatic neuroendocrine tumours.
abstract: BACKGROUND
  Pancreatic neuroendocrine tumours (pNETs) are rare and the majority of patients present with advanced disease. Such patients have limited treatment options. We conducted a systematic review of published clinical trials of non-surgical interventions in pNET, to understand the efficacy, safety and health related quality of life (HRQoL) outcomes from the current evidence base.
  
  
  METHODS
  Electronic databases and manual bibliographic searches were conducted to identify relevant studies. Data were extracted by two independent reviewers.
  
  
  RESULTS
  Forty seven clinical studies met the predefined inclusion criteria. The following interventions were included: targeted therapies (two RCTs and six single-arm studies), chemotherapy (two RCTs, one prospective nonrandomised, comparative study and 14 single-arm studies);somatostatin analogues (SSA) and radiolabeled SSA therapies (nine single-arm studies), liver-directed therapies (six single-arm studies), mixed treatment regimens (one RCT, four single-arm studies) and other interventions such as interferon and recombinant human endostatin (one single-arm study for each). The paucity of RCT data and lack of consistency in reporting validated study outcomes and differing patient inclusion criteria between studies made it difficult to compare the relative efficacy of therapies.
  
  
  CONCLUSIONS
  The majority of published studies assessing treatment regimens for the management of pNET are single arm, non-randomised studies, often enrolling a small number of patients and not reporting clinically meaningful outcomes. However data from recently conducted studies assessing targeted therapies indicate that it is possible to conduct adequately powered RCTs reporting standardised oncological endpoints in this rare cancer. Further, similarly robust studies should be conducted to define the optimal treatment algorithm.
authors.affiliation: Department of Medical Oncology, Christie Hospital NHS Foundation Trust, Manchester, UK. Electronic address: Juan.valle@christie.nhs.uk.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.affiliation: Department of Medical Oncology, Northern Ireland Cancer Centre, Belfast City Hospital, Belfast, UK. Electronic address: MartinEatock@bch.n-i.nhs.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Eatock
authors.affiliation: Pfizer UK, Tadworth, Surrey, UK. Electronic address: Benjamin.Clueit@Pfizer.com.
authors.forename: Ben
authors.initials: B
authors.lastname: Clueit
authors.affiliation: Pfizer UK, Tadworth, Surrey, UK. Electronic address: Zahava.gabriel@pfizer.com.
authors.forename: Zahava
authors.initials: Z
authors.lastname: Gabriel
authors.affiliation: Pfizer UK, Tadworth, Surrey, UK. Electronic address: roxanne.ferdinand@pfizer.com.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Ferdinand
authors.affiliation: Abacus International, 6 Talisman Business Centre, Talisman Road, Bicester, Oxfordshire OX26 6HR, UK. Electronic address: Stephen.mitchell@abacusint.com.
authors.forename: Stephen
authors.initials: S
authors.lastname: Mitchell
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D018358:Neuroendocrine Tumors / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000628:therapy*; D018714:Radiotherapy, Adjuvant / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Pancreatic neuroendocrine tumour; Systematic review