胃癌原发灶体积改变在胃癌术前化疗疗效评价中的应用价值

刘 坤, 李国立, 范朝刚, 汤黎明, 许 建

(1. 南京医科大学附属常州第二人民医院 普外科, 江苏 常州, 213003;南京军区南京总医院, 2. 普通外科研究所; 3. 医学影像科, 江苏 南京, 210002)



胃癌原发灶体积改变在胃癌术前化疗疗效评价中的应用价值

刘 坤1, 李国立2, 范朝刚2, 汤黎明1, 许 建3

(1. 南京医科大学附属常州第二人民医院 普外科, 江苏 常州, 213003;南京军区南京总医院, 2. 普通外科研究所; 3. 医学影像科, 江苏 南京, 210002)

目的 观察胃癌原发灶体积改变在胃癌术前化疗疗效评价中的应用价值。方法 回顾性分析150例接受术前化疗和D2胃癌根治术的患者的临床资料。参照Becker评分行病理学化疗反应评价。采用Kaplan-Meier法绘制生存曲线。观察化疗前后胃癌原发灶体积减小百分率与Becker评分及患者生存的关系。结果 化疗后胃癌原发灶体积较化疗前显著减小(P<0.001)。化疗后原发灶体积减少百分率与Becker评分密切相关(R=0.5672,P=0.002)。ROC曲线分析提示，化疗前后原发灶体积减少百分率对鉴别化疗有效与无效的患者有重要价值，曲线下面积(AUC)为0.845, 评价化疗有效的界值点被设定为体积减少达到55%。结论 胃癌原发灶体积减少程度可以应用于评价胃癌化疗疗效。

胃癌; 术前化疗; 体积测量; RECIST标准

胃癌居全球恶性肿瘤发病率的第4位和死亡率的第2位，每年新增病例近100万[1]。由于缺乏早期典型症状，大多数胃癌患者在确诊时已处于进展期[2]。与传统的术后化疗相比，术前新辅助化疗具有诸多优势[3]。实体瘤评效标准(RECIST)是目前最为常用的影像学疗效评价标准[4]。根据化疗前后靶病灶直径的改变，RECIST标准将化疗疗效分为完全缓解(CR)、部分缓解(PR)、疾病稳定(SD)和疾病进展(PD)4个等级。本研究通过回顾性分析胃癌患者的影像学资料、病理学资料及生存随访数据，观察胃癌原发灶体积改变在新辅助化疗疗效评价中的应用价值，现报告如下。

1 资料与方法

1.1 一般资料

回顾性分析2006年6月—2012年12月150例接受术前化疗和胃癌根治术患者的基本资料。入选标准: ① 经组织学检查证实的胃癌患者; ② 年龄30～70岁; ③ 明确诊断时肿瘤临床分期为T2～4N≥1M0; ④ ECOG体力状态评分为0或1; ⑤ 所有患者需完成2～3个疗程的术前化疗，并在化疗结束后3周内接受D2胃癌根治术; ⑥ 患者无严重的心、肝、肾功能障碍，无其他脏器恶性肿瘤; ⑦ 有完整的临床资料，包括化疗开始前CT、手术前CT、手术切除标本的病理学资料及随访资料。

1.2 影像学评价

所有患者均在第一次化疗前及接受手术治疗前行CT检查。检查前夜禁食、禁水，检查前0.5 h肌注东莨菪碱10 mg以减少胃肠蠕动，检查前5 min快速饮水1 000 mL使胃膨胀。常规仰卧位平扫+增强(西门子64排螺旋CT)，以西门子公司Volume软件测量化疗前后胃癌原发灶的体积，并计算体积变化百分率。

1.3 病理学评价

对术前化疗的病理学疗效评价参照Becker等在2003年提出的Becker评分进行[13]。根据化疗后残余肿瘤占整个肿瘤原发灶的比例，Becker评分1级(<10%肿瘤残余)和2级(10～50%肿瘤残余)视为化疗有效，3级(>50%肿瘤残余)判定为化疗无效。

1.4 统计学分析

采用SPSS 17.0软件进行统计分析，化疗前后原发灶体积变化采用Wilcoxon(配对样本)秩和检验。不同组别之间体积变化百分率的差异比较采用Mann-Whitney U检验。体积变化百分率与Becker评分之间的相关性采用Spearman相关性检验。应用ROC曲线分析的方法评价体积变化百分率在化疗有效性鉴别中的价值。Kaplan-Meier法绘制生存曲线，生存率的差异以Log-rank法检验。P<0.05为差异有统计学意义

2 结 果

2.1 化疗前后原发灶体积变化

2006年6月—2012年12月共150例符合条件的患者纳入该研究。化疗前后胃癌原发灶的体积分别为(74.2±59.6) cm3及(41.5±23.1) cm3, 化疗后原发灶体积较化疗前减小，差异有统计学意义(P<0.01)。

2.2 病理学化疗疗效评价结果

150例手术切除标本的Becker评分结果如下: 1级36例，2级74例，3级40例，共计化疗有效110例，无效40例。对化疗有效组患者而言，化疗前后原发灶体积减少百分率为(61.8±24.6)%，显著高于化疗无效组患者(29.4±21.7)%(P<0.01)。Spearman相关性分析提示，化疗前后原发灶体积减少百分率与Becker评分密切相关(R=0.5672,P=0.002)。ROC曲线分析提示，化疗前后原发灶体积减少百分率对于鉴别化疗有效与无效的患者有重要价值，曲线面积(AUC)为0.845 (95% CI: 0.778～0.913)。见图1。当界值点设定为体积减少55%时，约登指数可获得最大值，此时对应的敏感度为82.7%，特异性为67.5%。

2.3 生存分析

根据ROC曲线分析结果，作者将化疗后原发灶体积减小55%作为化疗有效的影像学标准。由此, 104位患者评判为化疗有效, 46位患者评判为化疗无效。化疗有效的患者的总体生存显著优于化疗无效的患者(P=0.0138)。见图2。

图1 ROC曲线分析评价胃癌原发灶体积变化百分率在化疗有效性的价值

图2 化疗有效组与化疗无效组患者术后生存率比较

3 讨 论

RECIST标准在评价胃肠道肿瘤化疗疗效时有着明显缺陷。首先，肿瘤并非标准的球体，因此某一方向直径的变化不能准确反映化疗前后肿瘤大小的改变[5]。其次，对胃肠道等空腔脏器而言，CT上其厚度及最大径随着胃肠充盈程度不同而改变，因此RECIST标准建议将胃肠道肿瘤原发灶纳入为“不可测量的病灶”，仅将转移灶(包括转移淋巴结和远处转移病灶)化疗前后的直径改变作为评价化疗疗效的依据[6-8]。由此，难以对无转移灶的T3～4N0M0患者进行准确的疗效评价。第三，临床上淋巴结反应性增生并非罕见，对于无远处转移灶的局部进展期胃癌患者而言，仅考虑淋巴结直径的变化而忽略化疗对肿瘤原发灶的影响，往往难以准确衡量化疗疗效。因此，对RECIST标准进行改进，建立更适合胃癌患者的影像学化疗评价标准有着重要意义[9-13]。

理想的影像学评价标准应同时具备准确、稳定和及时快速等要素。Beer等[14-15]揭示，化疗后2周左右病灶体积即可有明显变化，而直径变化一般需要7～8周。以体积变化来衡量化疗疗效已被应用于直肠癌[16]、肺转移灶[10]、肝转移灶[17]、膀胱癌[18]、及头颈部肿瘤[19]，并获得良好的临床评价。

本研究观察了局部进展期胃癌患者新辅助化疗后原发灶的体积变化。作者发现: ① 化疗后胃癌原发灶体积较化疗前明显减小; ② 原发灶体积减少百分率对于鉴别化疗有效与无效的患者有重要价值; ③ 化疗后原发灶体积减少百分率与患者预后有关。上述结果提示，原发灶体积减少程度可以应用于评价胃癌化疗疗效。

与RECISDT标准相比，以原发灶体积变化来评价化疗疗效有以下优势: ① 扩大了应用范围。对于T3～4N0M0的患者，虽然没有可测量的淋巴结和转移灶，作者可以通过胃癌原发灶的体积改变来评价新辅助化疗的效果。② 提高了准确度。首先，将原发灶纳入测量范围，而不是仅仅测量靶淋巴结和转移灶，有助于提高疗效评价的准确度；其次，肿瘤不是标准的球体，因此体积测量较RECIST标准的直径测量更准确反映肿瘤大小的变化。③ 与直径测量相比，体积测量有更好的稳定性(测量结果的可重复性)。④ 与直径测量相比，体积测量能更早地检测出肿瘤对化疗的反应。

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Value of primary tumor volumetry in predicting tumor response to preoperative chemotherapy in patients with gastric cancer

LIU Kun1, LI Guoli2, FAN Chaogang2, TANG Liming1, XU Jian3

(1.DepartmentofGeneralSurgery,ChangzhouSecondPeople′sHospitalAffiliatedtoNanjingMedicalUniversity,Changzhou,Jiangsu, 213003; 2.InstituateofGeneralSurgery; 3.DepartmentofMedicalImaging,NanjingGeneralHospitalofNanjingMilitaryCommand,Nanjing,Jiangsu, 210002)

Objective To observe the value of primary tumor volumetry in predicting tumor response to preoperative chemotherapy in gastric cancer patients. Methods A total of 150 gastric cancer patients who received preoperative chemotherapy and D2 radical resection were analyzed retrospectively. Pathologic tumor response was evaluated according to Becker score. The percentage change in primary tumor volume between pre-and post-chemotherapy was calculated, and correlation between pathologic tumor regression and survival quality was analyzed. Ability of primary tumor volumetry to distinguish pathologic responders and non-responders was evaluated by receiver operating characteristic (ROC) curve analysis. Results The volume of primary gastric lesion significantly decreased after neo-adjuvant chemotherapy (P<0.001). Percentage reduction rate of primary tumor volume in the pathologic responder group was significantly larger than the non-responder group. There was a significant association between primary tumor volume reduction rate and pathologic tumor regression grade (Becker score). ROC curve analysis showed that volume change of primary gastric lesion was a potential parameter to differentiate pathologic responders from non-responders (AUC=0.845), and the optimal cutoff level was determined to be a reduction of ≥ 55%. Furthermore, responders based on the volumetric criteria had a better overall survival than non-responders. Conclusion Primary tumor volumetry could be used to assess tumor response to preoperative chemotherapy in gastric cancer patients.

gastric cancer; preoperative chemotherapy; volumetric measurement; RECIST criteria

2016-09-27

江苏省常州市应用基础研究计划(CJ20130024); 解放军南京军区面上课题(12ma087)

R 735.2

A

1672-2353(2016)24-060-03

10.7619/jcmp.201624017