Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy

Abstract

BACKGROUND:In neoadjuvant chemotherapy for advanced esophageal cancers, complete tumor regression has been difficult to achieve, and tumor often remained after chemotherapy. However, the best method for evaluating the response to chemotherapy based on histopathologic examination of residual tumors has not been established.METHODS:Studied were 74 patients who received neoadjuvant chemotherapy (5‐fluorouracil, cisplatin, and doxorubicin), followed by surgery for advanced esophageal squamous cell carcinoma. The correlation between various histopathologic factors and clinical response with survival was examined, including the importance of tumor budding in the invasive front of tumors on clinical response and survival.RESULTS:Among 74 patients, 3 achieved a pathologic complete response, and 29 (41%) of 71 residual tumors demonstrated high‐grade budding in the invasive front. The 5‐year survival rate of patients with low‐grade budding tumors was 49%, compared with 17% for those with high‐grade budding (P < .001). Budding correlated inversely with good response, which was observed in 44 (60%) of 74 patients. Univariate analysis showed that pathologic tumor depth, number of lymph node metastases, pathologic stage, lymphatic invasion, budding and clinical response were significant prognostic factors. Multivariate analysis identified budding as the most important prognostic factor followed by number of lymph node metastases.CONCLUSIONS:The results of the current study indicated that tumor budding in the invasive front of tumors correlated significantly with clinical response and prognosis of patients with esophageal squamous cell carcinomas who received neoadjuvant chemotherapy. However, the mechanism of tumor budding in the invasion front of esophageal squamous cell carcinomas treated with chemotherapy was not clarified. Cancer 2009. © 2009 American Cancer Society.

A seemingly most effective target for early detection and intervention of prostate tumor invasion

“…Our findings of tumor cell budding from focally disrupted prostate tumor capsule are consistent with those of a number of previous studies in human esophageal and colorectal cancers, which detected a similar pattern and frequency of tumor cell budding, and revealed that tumors with budding cells were significantly correlated with invasion, metastasis, and worse prognosis [39][40][41]. The results of our gene expression profiling are also in line with those of a recent study, which showed that microdissected cells from the periphery and the center of the same ductal carcinoma in situ had a markedly different frequency and pattern in the expression of 22 genes, assessed with Atlas human Cancer 1.2 Arrays containing 1176 known genes [42].…”

Let-7 Expression Is a Significant Determinant of Response to Chemotherapy through the Regulation of IL-6/STAT3 Pathway in Esophageal Squamous Cell Carcinoma

“…All patients received neoadjuvant chemotherapy, which consisted of 2 courses of 5-fluorouracil (5-FU), cisplatin, and Adriamycin, using the following protocol: Cisplatin was administered at 70 mg/m 2 , Adriamycin was administered at 35 mg/m 2 intravenously on day 1, and 5-FU was administered continuously from days 1 to 7 at 700 mg/m 2 /d. Two courses of chemotherapy were provided after an interval of 4 weeks (8). The median follow-up period was 22.4 months.…”

“…Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery has emerged as a promising strategy for advanced esophageal cancer and in fact, good responders to such preoperative therapy show better survival (2,3). However, the reported response rate to cisplatin-based chemotherapy, which is widely used for esophageal cancer, is only modest, ranging from 25% to 48% (4-7) and nonresponders likely receive no survival benefit (8). The ability to predict the response to chemotherapy before treatment should limit the application of chemotherapy to selected patients who are likely to show some benefits, and allow tailoring such therapy to the individual patient with esophageal cancer.…”

Prognostic value of an inflammation-based score in patients undergoing pre-operative chemotherapy followed by surgery for esophageal cancer

“…Pre-operative chemotherapy administered at our hospital consisted of cisplatin, adriamycin and 5-fluorouracil (5-FU) (19). Cisplatin was administered at 70 mg/m 2 , adriamycin at 35 mg/m 2 by rapid intravenous infusion on Day 1; and 5-FU at 700 mg/m 2 administered by continuous intravenous infusion on Day 1-7.…”

“…The extent of viable residual carcinoma at the primary site was assessed semi-quantitatively, based on the estimated percentage of viable residual carcinoma in relation to the macroscopically identifiable tumor bed that was evaluated histopathologically. The percentage of viable residual tumor cells within the entire cancerous tissue was assessed as follows: grade 3, no viable residual tumor cells; grade 2, <1/3 residual tumor cells; grade 1b, 1/3-2/3 residual tumor cells; grade 1a, >2/3 residual tumor cells; grade 0, no significant response to chemotherapy (19,20). The extent of residual carcinoma in regional lymph nodes was not assessed.…”