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Significance of Histological Response to Preoperative Chemoradiotherapy for Pancreatic Cancer

Authors
  • White, Rebekah R.1
  • Xie, H. Bill2
  • Gottfried, Marcia R.2
  • Czito, Brian G.3
  • Hurwitz, Herbert I.3
  • Morse, Michael A.4
  • Blobe, Gerald C.4
  • Paulson, Erik K.5
  • Baillie, John4
  • Branch, M. Stanley4
  • Jowell, Paul S.1
  • Clary, Bryan M.4
  • Pappas, Theodore N.1
  • Tyler, Douglas S.1
  • 1 Duke University Medical Center, Department of Surgery, Durham, North Carolina, 27710 , Durham
  • 2 Duke University Medical Center, Department of Pathology, Durham, North Carolina , Durham
  • 3 Duke University Medical Center, Department of Radiation Oncology, Durham, North Carolina , Durham
  • 4 Duke University Medical Center, Department of Medicine, Durham, North Carolina , Durham
  • 5 Duke University Medical Center, Department of Radiology, Durham, North Carolina , Durham
Type
Published Article
Journal
Annals of Surgical Oncology
Publisher
Springer - Society of Surgical Oncology
Publication Date
Mar 03, 2005
Volume
12
Issue
3
Pages
214–221
Identifiers
DOI: 10.1245/ASO.2005.03.105
Source
Springer Nature
Keywords
License
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Abstract

BackgroundNeoadjuvant (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.MethodsSince 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.ResultsThe 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.ConclusionsHistological 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.

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