Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy

Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):195-200. doi: 10.1016/j.ijrobp.2006.04.026. Epub 2006 Jul 12.

Abstract

Purpose: To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

Methods and materials: A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level.

Results: Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p = 0.012 vs. odds ratio, 3.235; p < 0.001, respectively).

Conclusion: A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Capecitabine
  • Combined Modality Therapy / methods
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • ErbB Receptors / metabolism*
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Radiotherapy Dosage
  • Rectal Neoplasms / drug therapy
  • Rectal Neoplasms / metabolism*
  • Rectal Neoplasms / pathology*
  • Rectal Neoplasms / radiotherapy
  • Retrospective Studies

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • Deoxycytidine
  • Capecitabine
  • ErbB Receptors
  • Leucovorin
  • Fluorouracil