P-0211 The Prognostic Significance of Tumor Egfr Expression After Neoadjuvant Chemoradiation in Patients With Rectal Adenocarcinoma

Abstract

ABSTRACT Introduction The aim of the present study was to examine the prognostic significance of tumor epidermal growth factor receptor (EGFR) expression after neoadjuvant chemoradiation in patients with locally advanced rectal adenocarcinoma. Methods Between June 2000 and November 2006, 65 patients, 46 males and 19 females, median age 64 (range 41-75) years, with locally advanced rectal adenocarcinoma were treated. Twenty-two patients had clinical stage II and 43 patients had clinical stage III tumor. The anatomical localization was as follows: lower rectum ( 5-10 cm) 35 patients, and upper rectum (> 10 cm) 9 patients. The median pretreatment CEA level was 4.20 (range 0.20-62.39) μg/L. Neoadjuvant treatment consisted of 50.4 Gy/ 28 fractions external radiation with concomitant continuous 5-fluorouracil. Surgical resection was performed 4-6 weeks after the chemoradiation. EGFR expression in the resected specimens was assessed with immunohistochemistry. Disease-free survival (DFS) and overall survival (OS) were evaluated form the start of the treatment. Log-rank test and Cox regression were used to analyze the prognostic significance of studied parameter. Results Radical resection with microscopically negative margins (R0) was performed in 61 patients (27 patients sphincter-preserving resection and 34 patients abdomino-perineal resection) and resection with microscopic residual tumor (R1) in 4 patients (3 patients after sphincter-preserving resection and 1 patient after abdomino-perineal resection). The pathologic TNM stage after chemoradiation was as follows: with pathologic complete response 2 patients, microscopic residual tumor 2 patients, stage I 19 patients, stage II 26 patients, stage III 13 patients and stage IV 3 patients. All 3 patients with stage IV had liver metastases detected during surgery. Downstaging after preoperative chemoradiation was observed in 41 patients (63%). During the follow-up, recurrence occurred in 28 patients, and 34 patients died. At the time of analysis, 30 patients were alive without recurrence, and 1 patient was alive with recurrence. Five-year disease free survival (DFS) was 51% (95% CI: 39-63%) and 5-year overall survival (OS) was 55% (95% CI: 43-67%). The median follow-up after the end of treatment was 64 months (5.3 years). EGFR expression was as follows: score 0 in 18 patients, score 1 in 24 patients, score 2 in 14 patients, score 3 in 7 patients and insufficient specimen in 2 patients. Patients with an intense EGFR expression in the resected specimens after chemoradiation had significantly shorter DFS (p=0.04) and OS (p=0.03) in univariate Cox regression analysis. Intensity of EGFR expression tended to statistical significance on DFS (p=0.08) and OS (p=0.10) in multivariate analysis; while the most significant predictor here was the pathological stage after chemoradiation (p=0.01 both for DFS and OS). Conclusion The intensity of EGFR expression in the resected specimens after chemoradiation is associated with significantly shorter DFS and OS.