The changes of VEGF expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

Background: The aim was to examine the effect of neoadjuvant chemoradiation on vascular endothelial growth factor (VEGF) expression in patients (pts) with locally advanced rectal adenocarcinoma.

Materials and Methods: A total of 53 pts with rectal adenocarcinoma (38 men and 15 women) were retrospectively studied. Sixteen pts had clinical stage II and 37 pts had clinical stage III tumor. The anatomical localization was as follows: 19 pts lower rectum (<5cm from the anal verge), 28 pts middle rectum (>5–10cm), and 6 pts upper rectum (>10cm). All pts had a histologically verified adenocarcinoma in a pretreatment biopsy: 3 pts grade 1, 32 pts grade 2, and 18 pts grade 3. Grade in the resected specimens was as follows: 3 pts grade 1, 28 pts grade 2, and 20 pts grade 3. Neoadjuvant treatment consisted of 50.4 Gy/28 fractions external radiation with concomitant continuous 5-fluorouracil. All pts completed the planned dose of radiotherapy. Two pts did not complete the planned dose of chemotherapy, in both cases due to hematologic toxicity. Surgical resection was performed 4–6 weeks after the chemoradiation. VEGF expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry, semiquantitavely (score 0–3+).

Results: During chemoradiation 24 pts (45%) had decreased VEGF expression, 7 pts (13%) had an increase, inin 20 pts (38%) there was no change, and in 2 pts it was not possible to assess the dynamics of VEGF expression due to insufficient amount of tissue for immunohistochemical analysis. The median of follow-up was 75 months (6.3 years). Radical resection with microscopically negative margins (R0) was performed in 51 pts (22 patients sphincter-preserving resection and 29 pts abdominoperineal resection) and resection with microscopic residual tumor (R1) in 2 pts (1 pt after sphincter-preserving resection and 1 pt after abdominoperineal resection). The pathologic TNM stage after chemoradiation was as follows: with pCR 2 pts, microscopic residual tumor 2 pts, 16 pts stage I, 18 pts stage II, 12 pts stage III, and 3 pts stage IV. All 3 pts with stage IV had liver metastases detected during surgery. Downstaging after preoperative chemoradiation was observed in 34 pts (64%). During follow-up 24 pts had recurrence and 30 pts died. At the date of evaluation 22 pts were alive without recurrence and 1 pt was alive with recurrence. Five-year overall survival was 56% (95%CI: 43–70%). The coefficient of determination (R2) in Cox regression analysis was 0.0267. R2 in analysis of deviance was not significant (p=0.502).

Conclusions: The changes of VEGF expression after neoadjuvant chemoradiation in pts with rectal adenocarcinoma had no predictive or prognostic significance.

Acknowledgement: This study was supported by the research project UK-LF HK: PRVOUK P37/01.

No conflict of interest.