Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China.
World J Gastroenterol. 2012 Dec 21;18(47):7026-32. doi: 10.3748/wjg.v18.i47.7026.
To quantitatively assess the ability of double contrast-enhanced ultrasound (DCUS) to detect tumor early response to pre-operative chemotherapy.
Forty-three patients with gastric cancer treated with neoadjuvant chemotherapy followed by curative resection between September 2011 and February 2012 were analyzed. Pre-operative chemotherapy regimens of fluorouracil + oxaliplatin or S-1 + oxaliplatin were administered in 2-4 cycles over 6-12 wk periods. All patients underwent contrast-enhanced computed tomography (CT) scan and DCUS before and after two courses of pre-operative chemotherapy. The therapeutic response was assessed by CT using the response evaluation criteria in solid tumors (RECIST 1.1) criteria. Tumor area was assessed by DCUS as enhanced appearance of gastric carcinoma due to tumor vascularity during the contrast phase as compared to the normal gastric wall. Histopathologic analysis was carried out according to the Mandard tumor regression grade criteria and used as the reference standard. Receiver operating characteristic (ROC) analysis was used to evaluate the efficacy of DCUS parameters in differentiating histopathological responders from non-responders.
The study population consisted of 32 men and 11 women, with mean age of 59.7 ± 11.4 years. Neither age, sex, histologic type, tumor site, T stage, nor N stage was associated with pathological response. The responders had significantly smaller mean tumor size than the non-responders (15.7 ± 7.4 cm vs 33.3 ± 14.1 cm, P < 0.01). According to Mandard's criteria, 27 patients were classified as responders, with 11 (40.7%) showing decreased tumor size by DCUS. In contrast, only three (18.8%) of the 16 non-responders showed decreased tumor size by DCUS (P < 0.01). The area under the ROC curve was 0.64, with a 95%CI of 0.46-0.81. The effects of several cut-off points on diagnostic parameters were calculated in the ROC curve analysis. By maximizing Youden's index (sensitivity + specificity - 1), the best cut-off point for distinguishing responders from non-responders was determined, which had optimal sensitivity of 62.9% and specificity of 56.3%. Using this cut-off point, the positive and negative predictive values of DCUS for distinguishing responders from non-responders were 70.8% and 47.4%, respectively. The overall accuracy of DCUS for therapeutic response assessment was 60.5%, slightly higher than the 53.5% for CT response assessment with RECIST criteria (P = 0.663). Although the advantage was not statistically significant, likely due to the small number of cases assessed. DCUS was able to identify decreased perfusion in responders who showed no morphological change by CT imaging, which can be occluded by such treatment effects as fibrosis and edema.
DCUS may represent an innovative tool for more accurately predicting histopathological response to neoadjuvant chemotherapy before surgical resection in patients with locally-advanced gastric cancer.
定量评估双对比增强超声（DCUS）检测胃癌患者术前化疗早期肿瘤反应的能力。
分析 2011 年 9 月至 2012 年 2 月期间接受新辅助化疗后行根治性切除术的 43 例胃癌患者。氟尿嘧啶+奥沙利铂或 S-1+奥沙利铂的术前化疗方案在 6-12 周内进行 2-4 个周期。所有患者均在术前化疗前和后进行增强 CT 扫描和 DCUS 检查。采用实体瘤反应评价标准（RECIST 1.1）评估治疗反应。通过 DCUS 评估，由于肿瘤血管，对比期胃腺癌的增强外观与正常胃壁相比。根据 Mandard 肿瘤消退分级标准进行组织病理学分析，并作为参考标准。使用受试者工作特征（ROC）分析评估 DCUS 参数在区分组织病理学反应者与非反应者方面的有效性。
研究人群包括 32 名男性和 11 名女性，平均年龄为 59.7±11.4 岁。年龄、性别、组织学类型、肿瘤部位、T 分期和 N 分期均与病理反应无关。反应者的平均肿瘤大小明显小于非反应者（15.7±7.4cm 与 33.3±14.1cm，P<0.01）。根据 Mandard 标准，27 例患者被归类为反应者，其中 11 例（40.7%）通过 DCUS 显示肿瘤大小减小。相比之下，仅 16 例非反应者中的 3 例（18.8%）通过 DCUS 显示肿瘤大小减小（P<0.01）。ROC 曲线下面积为 0.64，95%CI 为 0.46-0.81。在 ROC 曲线分析中计算了几个截断点对诊断参数的影响。通过最大化 Youden 指数（灵敏度+特异性-1），确定了区分反应者和非反应者的最佳截断点，其具有最佳的 62.9%的灵敏度和 56.3%的特异性。使用该截断点，DCUS 区分反应者和非反应者的阳性和阴性预测值分别为 70.8%和 47.4%。DCUS 对治疗反应评估的总体准确性为 60.5%，略高于 RECIST 标准的 CT 反应评估的 53.5%（P=0.663）。虽然优势并不具有统计学意义，但可能是由于评估的病例数量较少。DCUS 能够识别出在 CT 成像显示无形态变化的反应者中灌注减少的情况，这种情况可能被纤维化和水肿等治疗效果所阻断。
DCUS 可能是一种新的工具，可在局部进展期胃癌患者行手术切除前更准确地预测新辅助化疗的组织病理学反应。
