Correlation of tumor regression grade (TRG), circumferential margin (CM), and epidermal growth factor receptor expression with disease-free survival (DFS) in locally advanced rectal cancer patients (LARC) treated with preoperative radiochemotherapy (preCh-RT).

Abstract

e14076 Background: EGFR overexpression has been associated with radioresistance and poor prognosis. The aim of this study was to determine the EGFR expression rate in LARC and to analyze if EGFR expression could predict pathological tumor response to pre Ch-RT. We also evaluate EGFR as prognostic factor (PF) for DFS and compare to other PFs as CM or TRG. Methods: Between April 2004 and October 2008, 92patients were included. Treatment consisted of preoperative pelvic radiotherapy (45Gy+ 5.4 Gy boost, at 180 cGy per fraction) and capecitabine (825 mg/m2/BID during radiotherapy). Surgical resection (TME) was performed 6–8 weeks after preCh-RT finished . Immunohistochemistry for EGFR was determined at the preradiation diagnostic biopsy. Immunostaining was performed using EGFR monoclonal antibody (Biogenex, MU 207-UC). Immunohistochemical staining was evaluated according to extension and intensity. We defined positive staining (EGFR+) as extension of 10% or more. TRG was determined by Mandard's criteria. Follow up of the series: 50 months (26-80 m) Results: Preoperative treatment resulted in pathologic complete remission in 13 patients (14%), and downstaging in 43 patients. EGFR+ was observed in 62 of 92 tumors (67.4%) and was associated with neither clinical tumor stage nor clinical nodal stage. TRG 1-2 was observed in 56% of low-EGFR expression (0-1) versus 36% of high- EGFR expression (2-3), p=0.09. According to TRG, 3-years DFS was 100% vs 71% for TRG 0-1 and TRG 2-3 (p=0.001) , respectively. Regarding CM, 3-year DFS was 86% vs 70% for CM<1mm vs >1mm (p=0.1). Finally, 3-year DFS was 85% vs 81% for EGFR negative (0-1) vs positive (2-3) (p=0.5). Conclusions: Although EGFR is significantly expressed in locally advanced rectal tumors, its expression is not predictive factor for response to preCh-RT. Based in our results, TRG is the strongest prognostic factor for clinical outcome patients treated with radiotherapy and concomitant capecitabine.