title: Protocol of the PANCALYZE trial: a multicenter, prospective study investigating the tumor biomarkers CXCR4, SMAD4, SOX9 and IFIT3 in patients with resected pancreatic adenocarcinoma to predict the pattern of recurrence of the disease.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies today with an urgent need for novel therapeutic strategies. Biomarker analysis helps to better understand tumor biology and might emerge as a tool to develop personalized therapies. The aim of the study is to investigate four promising biomarkers to predict the clinical course and particularly the pattern of tumor recurrence after surgical resection.
  
  
  
  Patients undergoing surgery for PDAC can be enrolled into the PANCALYZE trial. Biomarker expression of CXCR4, SMAD4, SOX9 and IFIT3 will be prospectively assessed by immunohistochemistry and verified by rt.-PCR from tumor and adjacent healthy pancreatic tissue of surgical specimen. Immunohistochemistry expression pattern of all four biomarkers will be combined into a single score. Beginning with the hospital stay clinical data from enrolled patients will be collected and followed. Different adjuvant chemotherapy protocols will be used to create subgroups. The combined biomarker expression score will be correlated with the further clinical course of the patients to test the hypothesis if CXCR4 positive, SMAD4 negative, SOX9 positive, IFIT3 positive tumors will predominantly develop metastatic spread.
  
  
  
  Pancreatic cancer is associated with different patterns of progression requiring personalized therapeutic strategies. Biomarker expression analysis might be a tool to predict the pattern of tumor recurrence and discriminate patients that develop systemic metastatic disease from those with tumors that rather develop local recurrence over time. This data might lead to personalized adjuvant treatment decisions as patients with tumors that stay localized might benefit from adjuvant local therapies like radiochemotherapy as compared to those with systemic recurrence who would benefit exclusively from chemotherapy. Moreover, the pattern of propagation might be a predefined characteristic of pancreatic cancer determined by the genetic signature of the tumor. In the future, biomarker expression analysis could be performed on tumor biopsies to develop personalized therapeutic pathways right after diagnosis of cancer.
  
  
  
  German Clinical Trials Register, DRKS00006179 .
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany. felix.popp@uk-koeln.de.
authors.forename: Felix C
authors.initials: FC
authors.lastname: Popp
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Popp
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Betzler
authors.affiliation: Institute for Biometrics and Medical Informatics, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kropf
authors.affiliation: Clinic for General, Visceral and Vascular Surgery, University Clinic Magdeburg, Magdeburg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Garlipp
authors.affiliation: Department of General and Visceral Surgery, Vivantes Klinikum im Friedrichshain, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Benckert
authors.affiliation: Department of Pathology, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
authors.affiliation: Institute for Quality Control in Operative Medicine, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Lippert
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Christiane J
authors.initials: CJ
authors.lastname: Bruns
mesh_terms: D006801:Humans; D014408:Biomarkers, Tumor / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000453:epidemiology / Q000378:metabolism / Q000601:surgery; D011446:Prospective Studies; D019718:Receptors, CXCR4 / Q000032:analysis; D051901:Smad4 Protein / Q000032:analysis; D055758:SOX9 Transcription Factor / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; C116468:IFIT3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D019718:Receptors, CXCR4; D051901:Smad4 Protein; C497796:SMAD4 protein, human; C527932:SOX9 protein, human; D055758:SOX9 Transcription Factor
keywords: Biomarker analysis; Clinical test development; Immunohistochemistry; Pancreatic ductal adenocarcinoma; Pattern of recurrence; Personalized therapy; Prediction of outcome; Prognosis of pancreatic cancer, outcome; Rt.-PCR; Surgery