title: Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design.
abstract: BACKGROUND
  Methodological limitations of prior studies have prevented progress in the treatment of patients with borderline resectable pancreatic adenocarcinoma. Shortcomings have included an absence of staging and treatment standards and pre-existing biases with regard to the use of neoadjuvant therapy and the role of vascular resection at pancreatectomy.
  
  
  METHODS
  In this manuscript, we review limitations of studies of borderline resectable PDAC reported to date, highlight important controversies related to this disease stage, emphasize the research infrastructure necessary for its future study, and present a recently-approved Intergroup pilot study (Alliance A021101) that will provide a foundation upon which subsequent well-designed clinical trials can be performed.
  
  
  RESULTS
  We identified twenty-three studies published since 2001 which report outcomes of patients with tumors labeled as borderline resectable and who were treated with neoadjuvant therapy prior to planned pancreatectomy. These studies were heterogeneous in terms of the populations studied, the metrics used to characterize therapeutic response, and the indications used to select patients for surgery. Mechanisms used to standardize these and other issues that are incorporated into Alliance A021101 are reviewed.
  
  
  CONCLUSIONS
  Rigorous standards of clinical trial design incorporated into trials of other disease stages must be adopted in all future studies of borderline resectable pancreatic cancer. The Intergroup trial should serve as a paradigm for such investigations.
authors: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. mhgkatz@mdanderson.org
authors: Matthew H G
authors: MH
authors: Katz
authors: Robert
authors: R
authors: Marsh
authors: Joseph M
authors: JM
authors: Herman
authors: Qian
authors: Q
authors: Shi
authors: Eric
authors: E
authors: Collison
authors: Alan P
authors: AP
authors: Venook
authors: Hedy L
authors: HL
authors: Kindler
authors: Steven R
authors: SR
authors: Alberts
authors: Philip
authors: P
authors: Philip
authors: Andrew M
authors: AM
authors: Lowy
authors: Peter W T
authors: PW
authors: Pisters
authors: Mitchell C
authors: MC
authors: Posner
authors: Jordan D
authors: JD
authors: Berlin
authors: Syed A
authors: SA
authors: Ahmad
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic / Q000592:standards*; D006801:Humans; D020360:Neoadjuvant Therapy; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D018579:Patient Selection; D012107:Research Design / Q000592:standards*