Capecitabine-based Neoadjuvant Chemoradiation Therapy in Locally-advanced Rectal Cancer

PURPOSE: The aim of the study was to evaluate the efficacy and the toxicity of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally-advanced, resectable rectal cancer. METHODS: Thirty-five patients with locally-advanced rectal cancer (cT3/4, N-/+) were treated with capecitabine (825 mg/m2, twice daily for 7 days/wk) and concomitant RT (50.4 Gy/28 fractions). Surgery was performed 6-8 wk after completion of the chemoradiation followed by 4-6 cycles of adjuvant capecitabine monotherapy (1,250 mg/m2, twice daily for 14 days every 3 wk). RESULTS: The chemoradiation program was completed in all but 2 patients, for whom both capecitabine and RT were interrupted for 2 wk because of grade-3 diarrhea. A R0 resection under the principle of total mesorectal excision (low anterior resection, 26; intersphincteric resection, 6; abdominoperineal resection, 2) was performed in all but one patient with a low anterior resection with positive circumferential margin (R1). Primary tumor and node downstaging occurred in 57% and 60% of patients, respectively. The overall rate of downstaging, including both the primary tumor and node, was 77% (27 patients). A pathological complete response of the primary tumor was achieved in 4 patients (11%). No patient had grade-4 toxicity, and the only grade-3 toxicity developed was diarrhea in 2 patients (6%) during chemoradiation. During a median follow-up of 38 mo, distant metastases developed in 4 patients (multiple lung metastases, 2; aortocaval nodal metastases, 2), and another 2 patients showed local recurrence. The three-year disease-free survival was 83%. CONCLUSION: This study suggests that preoperative capecitabine-based chemoradiation therapy is an effective and safe treatment modality for the tratment of locally-advanced, resectable rectal cancer.

Intensity of Tumor Budding as an Index for the Malignant Potential in Invasive Rectal Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to quantitatively assess the intensity of tumor budding in rectal carcinoma and to determine how it correlates with the malignant potential. MATERIALS AND METHODS: Intensities of the tumor budding at the invasive front of the surgical specimens from 90 patients (male, 51) with well- or moderately- differentiated rectal carcinoma were investigated. Differences in the budding intensity among pathologic variables were compared, and recurrences and survivals were analyzed in accordance with degree of the budding intensity. The patients ranged in age from 33 to 75 years (mean, 55.4) with the median follow-up being 43 months (range, 12~108). RESULTS: Tumor budding was identified in 89 patients (98.9%) with a mean intensity of 7.5+/-5.3. The budding intensity was significantly higher in tumors with lymphatic invasion (p=0.0081), blood vessel invasion (p<0.0001), and perineural invasion (p=0.0013) than in those tumor without these findings. It became significantly higher with the increase in nodal stage (p<0.0001). The intensity of tumor budding in patients with relapse (29 patients) was significantly higher than that in patients without relapse (6.2+/-5.0 vs. 10.2+/-4.9; p=0.0005), but this difference in the intensity was observed only for the node-positive patients (8.0+/-3.4 vs. 11.9+/-5.1; p=0.0064). When the patients were stratified into two groups on either side of the mean of the intensity, the higher intensity group showed a significantly less favorable disease- free (DFS) and overall survival (OS) (p=0.0026 and 0.0205, respectively). Based on the multivariate analysis, the nodal stage and the intensity of budding proved to be the independent variables associated with DFS (p=0.023 and 0.03, respectively). CONCLUSION: Tumor budding at the invasive margin is a reliable pathologic index that indicates a higher malignant potential and a less favorable prognosis for patients with advanced rectal carcinoma.