Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer

Rebekah R. White, H. Bill Xie, Marcia R. Gottfried, Brian G. Czito, Herbert I. Hurwitz, Michael A. Morse, Gerald C. Blobe, Erik K. Paulson, John Baillie, M. Stanley Branch, Paul S. Jowell, Bryan M. Clary, Theodore N. Pappas, Douglas Tyler

Research output: Contribution to journalArticle

110 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)214-221
Number of pages8
JournalAnnals of Surgical Oncology
Volume12
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Fingerprint

Chemoradiotherapy
Pancreatic Neoplasms
Residual Neoplasm
Tumor Burden
Neoplasms
Survival
Necrosis
Adjuvant Chemoradiotherapy
Epidermal Growth Factor Receptor
Adenocarcinoma
Fibrosis
Biomarkers
Lymph Nodes
Staining and Labeling
Biopsy

Keywords

  • Chemoradiotherapy
  • Histological response
  • Neoadjuvant therapy
  • Pancreatic cancer

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer. / White, Rebekah R.; Xie, H. Bill; Gottfried, Marcia R.; Czito, Brian G.; Hurwitz, Herbert I.; Morse, Michael A.; Blobe, Gerald C.; Paulson, Erik K.; Baillie, John; Branch, M. Stanley; Jowell, Paul S.; Clary, Bryan M.; Pappas, Theodore N.; Tyler, Douglas.

In: Annals of Surgical Oncology, Vol. 12, No. 3, 03.2005, p. 214-221.

Research output: Contribution to journalArticle

White, RR, Xie, HB, Gottfried, MR, Czito, BG, Hurwitz, HI, Morse, MA, Blobe, GC, Paulson, EK, Baillie, J, Branch, MS, Jowell, PS, Clary, BM, Pappas, TN & Tyler, D 2005, 'Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer', Annals of Surgical Oncology, vol. 12, no. 3, pp. 214-221. https://doi.org/10.1245/ASO.2005.03.105
White, Rebekah R. ; Xie, H. Bill ; Gottfried, Marcia R. ; Czito, Brian G. ; Hurwitz, Herbert I. ; Morse, Michael A. ; Blobe, Gerald C. ; Paulson, Erik K. ; Baillie, John ; Branch, M. Stanley ; Jowell, Paul S. ; Clary, Bryan M. ; Pappas, Theodore N. ; Tyler, Douglas. / Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer. In: Annals of Surgical Oncology. 2005 ; Vol. 12, No. 3. pp. 214-221.
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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.",
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AU - Xie, H. Bill

AU - Gottfried, Marcia R.

AU - Czito, Brian G.

AU - Hurwitz, Herbert I.

AU - Morse, Michael A.

AU - Blobe, Gerald C.

AU - Paulson, Erik K.

AU - Baillie, John

AU - Branch, M. Stanley

AU - Jowell, Paul S.

AU - Clary, Bryan M.

AU - Pappas, Theodore N.

AU - Tyler, Douglas

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