原发灶肿瘤体积对局部进展期直肠癌新辅助放化疗后病理完全反应的预测价值

Value of primary gross tumor volume in predicting pathologic complete response of locally advanced rectal cancer following neoadjuvant chemoradiotherapy

目的:探讨用原发灶大体肿瘤体积(GTV)预测局部进展期直肠癌(LARC)患者行新辅助放化疗(nCRT)后病理完全缓解(pCR)可行性。方法:回顾中南大学湘雅医院胃肠外科2009年3月—2015年12月行nCRT后予以根治性切除的LRAC患者107例资料,分析LARC患者行nCRT后到达pCR的临床预测因素,免疫组化检测患者肿瘤组织中直肠癌干细胞标志物CD133的表达,并分析原发灶GTV与直肠癌干细胞的关系。结果:107例LARC患者中,25例(23.36%)获pCR。LARC患者的原发灶GTV与肿瘤原发灶沿肠纵轴长度(r=0.580,P<0.001)及肿瘤原发灶最大径(r=0.608,P<0.001)均成正相关,但pCR患者与非pCR患者间仅在原发灶GTV(P=0.024)、nCRT前血清CEA水平(P=0.020)及多药化疗方案(P=0.05)方面存在明显差异。ROC曲线确定原发灶GTV判断肿瘤反应的最佳截点值为70.29 cm^3。Logistic回归分析显示,小原发灶GTV(<70 cm^3)(P=0.019)与多药联合化疗(P=0.032)LRAC患者nCRT后pCR的独立促进因素;大原发灶GTV(≥70 cm^3)的患者肿瘤组织CD133表达量明显高于小原发灶GTV(<70 cm^3)的患者(P=0.017)。结论:原发灶GTV可作为LARC患者行nCRT后pCR的独立预测因素,原发灶GTV大者pCR率低,原因可能部分与原发灶GTV越大肿瘤中的肿瘤干细胞量越高有关。

Objective： To investigate the feasibility of using primary gross tumor volume （GTV） for predicting the pathologic complete response （pCR） to neoadjuvant chemoradiotherapy （nCRT） in patients with locally advanced rectal cancer （LARC）. Methods： The data of 107 LARC patients undergoing nCRT followed by radical surgery in Department of Gastrointestinal Surger Xiangya Hospital of Central South University between March 2009 and December 2015 were reviewed. The factors for predicting pCR in LARC patients after nCRT were determined. The expressions of CD133 in the tumor specimens of these patients were measured by immunohistochemical staining, and then the relationship between primary GTV and rectal cancer stem cells was analyzed. Results： In the 107 LARC patients, pCR was achieved in 25 cases （23.36%）. The primary GTV was positively correlated with the length along the longitudinal axis of the bowel （r=0.580, P〈0.001） and maximal diameter （r=0.608, P〈0.001） of the primary tumor, while the significant differences between pCR patients and non-pCR patients were only found in primary GTV （P=0.024）, serum CEA level before nCRT （P=0.020）, and multiple- drug combined chemotherapy （P=0.05）. The optimal cut-offvalues for primary GTV to estimate the response of tumor was 70.29 cm3. The results of Logistic regression analysis showed that the small primary GTV （〈70 cm3） （P=0.019） and multiple-drug combined chemotherapy （P=0.032） were independent promotion factors for LARC patients to achieve p CR after nCRT. The CD 133 expression in the tumor tissues of patients with large primary GTV （≥70 cma） was significantly higher than that in patients with small primary GTV （〈70 cm3） （P=0.017）. Conclusion： Primary GTV can be used as an independent predictive factor for pCR in LARC patients after nCRT. Big primary GTV is associated with low pCR rate, which is probably due to the bigger the primary GTV, the larger the amount of cancer stem cells in the tumor.