title: Disseminated tumor cells in pancreatic cancer-an independent prognosticator of disease progression and survival.
abstract: Pancreatic cancer is one of the most devastating cancers with a 6-month median survival and a 5-year survival rate of 3-5%. Still important aspects of its aggressive biology remain elusive and advanced therapeutic regimens have not been substantially successful. We investigated the prognostic role of disseminated tumor cells (DTC) in bone marrow, a reservoir for early DTC potentially contributing to metastatic progression, of pancreatic cancer patients. After exclusion of patients with different postsurgery diagnosis or missing DTC status (n = 40) a total of 175 patients remained for final analyses. One-hundred and nineteen patients were male and 96 female with a median age of 67 years, 96 patients underwent complete resection. Bone marrow aspirates taken at primary surgery were analyzed for DTC by an immunocytochemical cytokeratin assay and correlated to survival data. Overall 13.7% of patient samples (24/175) harbored DTC in their bone marrow. Histopathological parameters did not correlate significantly. Univariate survival analysis revealed a borderline significant correlation between DTC and decreased progression-free survival (p = 0.069), and was significant for overall survival (p = 0.036). Regarding patients with resected tumors, the respective p-values were 0.058 for progression-free and 0.016 for overall survival. Importantly, the prognostic influence was independent from other risk factors as shown by multivariate analyses for progression-free (p = 0.030, HR: 2.057; CI (95%): 1.073-3.943) and overall survival (p = 0.006, HR: 2.283; CI (95%): 1.260-4.135). The presence of DTC in bone marrow is a strong and independent prognostic factor of survival in patients with pancreatic cancer. Thus, bone-targeting may be a new future therapeutic option for DTC-positive patients.
authors.affiliation: Department of General, Visceral, and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Germany. k.effenberger@uke.de
authors.forename: Katharina E
authors.initials: KE
authors.lastname: Effenberger
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schroeder
authors.forename: Christine
authors.initials: C
authors.lastname: Eulenburg
authors.forename: Matthias
authors.initials: M
authors.lastname: Reeh
authors.forename: Michael
authors.initials: M
authors.lastname: Tachezy
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Vashist
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
mesh_terms: D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis