title: Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer.
abstract: BACKGROUND
  Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection.
  
  
  METHODS
  Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods.
  
  
  RESULTS
  The estimated overall survival (median +/- SE) in the entire group of patients undergoing resection was 23 +/- 4.2 months, with an estimated 3-year survival of 37% +/- 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation.
  
  
  CONCLUSIONS
  Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.
authors.affiliation: Department of Surgery, Duke University Medical Center, Box 3118, Durham, North Carolina 27710, USA.
authors.forename: Rebekah R
authors.initials: RR
authors.lastname: White
authors.forename: H Bill
authors.initials: HB
authors.lastname: Xie
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Gottfried
authors.forename: Brian G
authors.initials: BG
authors.lastname: Czito
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Blobe
authors.forename: Erik K
authors.initials: EK
authors.lastname: Paulson
authors.forename: John
authors.initials: J
authors.lastname: Baillie
authors.forename: M Stanley
authors.initials: MS
authors.lastname: Branch
authors.forename: Paul S
authors.initials: PS
authors.lastname: Jowell
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Clary
authors.forename: Theodore N
authors.initials: TN
authors.lastname: Pappas
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Tyler
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents