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Ann Thorac Surg:男女有别!食管癌新辅助放化疗后手术女性应答好

2017-08-26 陶白 肿瘤资讯

8月22日,《Annals of Thoracic Surgery》上发表了一项由梅奥诊所普通胸外科进行的研究。研究显示,相比男性,罹患食管癌的女性对新辅助放化疗后行手术具有更好的应答,并且出现肿瘤复发的可能性低。

8月22日,《Annals of Thoracic Surgery》上发表了一项由梅奥诊所普通胸外科进行的研究。研究显示,相比男性,罹患食管癌的女性对新辅助放化疗后行手术具有更好的应答,并且出现肿瘤复发的可能性低。为此,该研究作者K. Robert Shen博士接受了相关媒体采访并点评:

在美国,食管癌仅占确诊癌症的1%,然而它却是一种致命性很强的疾病,是世界上癌症相关死亡的第6大死因和第8种最常见的癌症。食管腺癌的发病率已经大幅增加,受影响的男性患者数比女性高3~4倍。尽管存在性别差异,但是美国每年新确诊病例多数都为局部晚期病例。以经验来看,仅手术治疗的5年生存率仅为10%~20%。新辅助放化疗(nCRT)后行手术治疗已经成为局部晚期食管癌的标准治疗方法,与仅手术相比,该方法可改善局部控制、无疾病生存率和总生存率。

5年生存率无显着差异

明尼苏达州罗切斯特市梅奥诊所普通胸外科医生K. Robert Shen博士进行了一项最新且迄今为止规模最大的研究。此研究中,所有患者都为局部晚期食管癌并进行了食管胃切除术,并且接受了标准疗法——nCRT。

研究显示,在食管癌的治疗中,女性比男性有更好的应答。不幸的是,对nCRT较高完全和接近完全的病理学应答率优势并未给女性带来更高的生存率:女性和男性的总体5年生存率无显着性差异,但是女性生存率具有更好的趋势(52.1% vs 44%;P=0.53)。

Shen博士向Medscape医学新闻透露:“我们相信,在一个更大型的数据集中,我们将会观察到女性和男性的生存率会出现统计学着性差异。”

性别差异仍存

然而,该研究在其他方面却显示出了性别差异,展现了对女性的利好信息。

首先,女性比男性出现肿瘤复发的可能性低。

Shen博士表示,其次,在食管癌的其他方面,也确定了存在性别差异。他说:“食管癌对男性和女性会造成不同的影响,这在肿瘤生物学和遗传学上已经发映出差异。男性进展为食管癌的风险更高,女性对局部晚期食管癌的治疗具有更好的应答。”Shen博士指出,性激素(如雌激素)无论是以内源形式存在还是因替代疗法造成,其影响会在该差异中起到重要作用。

另外,Shen博士补充道,胃癌、肝细胞癌和结直肠癌也是发病率在男性中较高而生存率却在女性中较高的其他癌种。

大样本量更具说服力

其他研究已经表明,对于食管癌,与较小病理学(CP)应答相比,完全CP应答与生存率的改善相关,因此CP应答具有很重要的临床意义。其中,CP应答的定义为,nCRT和手术后食管和淋巴结都无疾病(T0N0期)。

然而,Shen博士指出,早期的研究中,性别与实现CP应答能力之间的相关性数据有限。因此,该研究团队进行了这项新研究。

Shen博士表示,新研究结果比更早期进行的研究结果(Ann Thorac Surg. 2009;87:392-399)更有意义。之前的那项研究中,研究者调查了食管癌结局中的性别差异,但是研究因女性太少(20例)而不能与男性(142例)进行比较,从而造成了说服力不强。

研究细节

在这项新研究中,梅奥诊所的研究团队回顾性调查了1990~2013年在3家梅奥中心(明尼苏达,佛罗里达,亚利桑那)nCRT后进行手术的145例女性患者。这些女性患者与221例男性对照患者进行了比较,并调整了年龄、治疗前临床分期、组织学类型和手术时间。

nCRT由两周期的化疗和同步放疗组成。化疗方案为5-氟尿嘧啶连续输注96小时(1000mg/m2,第1~4天、第1~5周)和顺铂(75mg/m2/d)每天推注1小时(第1周和第5周的第1天)。同步放疗包括28个分割剂量(180 cGy),每周5天,总剂量为5040 cGy。同时,nCRT后有4~6周的恢复期。

女性患者的中位年龄为64岁,男性患者为61岁。多数的食管癌组织学类型为腺癌(女性72%,男性87%),其余为鳞状细胞癌(女性28%,男性13%)。

研究表明,与男性(103例,47%)相比,女性患者更可能实现对nCRT的CP应答或接近完全病理学(NCP)应答(84例,58%;P=0.03)。

中位随访4.2年期间,女性患者的无复发生存率为71.7%,男性患者为55.4%。

与女性相比,男性患者复发风险增加80%(HR,1.80;95% CI,1.15~2.68;P=0.008)。

同时,研究也证实了,对诱导治疗出现较强应答与无复发生存率的改善相关,并独立于患者性别。CP应答或NCP应答患者的无复发生存率为75.5%(95% CI,67.8~83.0),而部分病理学(PP)应答者则为44.8%(95% CI,35.8~55.3;P=0.001)。

研究者指出,研究所采用的方法学是重要的。“我们的研究所采用的方法学是将女性和男性患者基于某些特征进行了配对,从而消除了可能的混杂因素。这项研究也是唯一一项使用该方法学的研究。”Shen博士在一份新闻声明中说。

然而,研究也存在局限性,其主要局限之一为,研究为非随机回顾性研究。患者为异质性,并且男性以腺癌为主,女性以鳞状细胞癌为主。将来需要更大样本量的研究,并且需要证实两性别间食管癌临床表现的更明确趋势。

以下是这项研究的关键性结果

CP应答:

女性44例(30%),男性57例(25%)。

NCP应答:

女性40例(28%),男性46例(20%)。

PP应答:

女性61例(42%),男性118例(53%)。

5年生存率:

女性为52.1%(95% CI,42.9~63.3),男性为44.0%(95% CI,37.1~52.3;P=0.53)。




男性和女性的总生存率

复发率:

总体复发率为32%(116例,男性69例,女性38例),中位复发时间为292天。55例男性和28例女性患者远处复发,23例男性和10例女性局部复发(P=0.008)。男性患者比女性患者复发风险高80%(HR,1.8;95% CI,1.15~2.68;P=0.008)。总体5年无复发生存率为47%,其中女性为71.7%(95% CI,60.8~81.3),男性为55.4%(95% CI,47.6~63.8;P=0.008)。



男性和女性的无复发生存率

复发的风险因素:

单变量分析显示,男性性别和PP应答都与复发风险的增加相关(HR,1.76;95% CI,1.15~2.68,P=0.009;HR,2.96;95% CI,1.98~4.43,P=0.001)。


对nCRT的不同病理学应答的无复发生存率

原始出处:Phillip G. Rowse, Dawn E. Jaroszewski, Mathew Thomas, et al. Sex Disparities After Induction Chemoradiotherapy and Esophagogastrectomy for Esophageal Cancer. the Annals of Thoracic Surgery. Jan 21–25, 2017.

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    2018-07-22 yyj062
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    2017-08-28 yzh399
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    2017-08-28 zhouqu_8

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