携带EGFR突变的非小细胞肺癌软脑膜转移(LM)更常见,且对TKI治疗反应好

2016-08-18 MedSci MedSci原创

广东省肺癌研究所、广东省人民医院吴一龙教授团队近日在《胸部肿瘤学杂志》(J Thor Oncol,JTO)发表研究论文,研究发现,在表皮生长因子受体(EGFR)基因突变非小细胞肺癌(NSCLC)患者中,柔脑膜转移(LM)更为常见。与未接受酪氨酸激酶抑制剂(TKI)治疗的患者相比,接受TKI治疗者的总生存(OS)期更长,提示TKI治疗LM的有效性。吴一龙教授柔脑膜是覆盖大脑的薄膜,包括蛛网膜和软脑膜

广东省肺癌研究所、广东省人民医院吴一龙教授团队近日在《胸部肿瘤学杂志》(J Thor Oncol,JTO)发表研究论文,研究发现,在表皮生长因子受体(EGFR)基因突变非小细胞肺癌(NSCLC)患者中,柔脑膜转移(LM)更为常见。与未接受酪氨酸激酶抑制剂(TKI)治疗的患者相比,接受TKI治疗者的总生存(OS)期更长,提示TKI治疗LM的有效性。



吴一龙教授

柔脑膜是覆盖大脑的薄膜,包括蛛网膜和软脑膜。肿瘤细胞转移到颅内结构和脑脊液(CSF)时,LM随之发生。LM是肺癌患者严重的并发症且与较差的生存期相关,其发生率为10%~26%。LM的治疗策略包括EGFR-TKI,化疗,全脑放疗(WBRT),鞘内化疗(ITC),手术和脑室腹腔分流术(VP),然而LM治疗仍充满挑战且尚无标准策略。EGFR TKI的应用显著延长了EGFR突变及频繁突变患者的生存期。

  • 吴一龙教授在采访中谈到:

“脑膜转移是目前肺癌治疗中最棘手的临床问题,我们从2011年就开始这方面的研究,第一篇文献是一项Ⅱ期研究,已发表在Ann Oncol上。主要是想探讨:为什么近年来脑膜转移会多见,是否与EGFR TKI的应用有关,还是与EGFR突变有关。治疗的方法应是首选哪一种?在做转化研究的同时,我们同时关注收集了所有的病例,这应该是目前国际上最大宗的脑膜转移的研究。”

研究者回顾性筛查了2011年1月至2015年6月广东省肺癌研究所、广东省人民医院的5387例NSCLC患者,以研究LM的NSCLC患者EGFR基因突变率,治疗情况及临床结局。查阅病历获取人口学资料、肿瘤相关特征和主要治疗方法。已知EGFR基因状态的患者通过CSF细胞学或增强MRI检测的筛查LM。OS期为从确诊LM到死亡或者随访结束的时间。OS以Kaplan-Meier法计算并展示95%可信区间OS中位值。

结果显示,5387例患者中有3775例患者接受了EGFR基因检测,其中1258例确诊EGFR突变阳性,2517例为EGFR野生型。5387例患者中,LM的发生率为3.4%(184/5387)。然而携带EGFR突变基因的患者中,LM发生率为9.4%(118/1258),显著高于EGFR基因野生型患者(1.7%,42/2517)(χ2= 122.9, P<0.001)。118例EGFR突变患者中,109例为常见突变,其中外显子19缺失突变53例,21号外显子L858R点突变56例。

与未接受TKI治疗相比,LM患者接受TKI治疗后有更长的OS期( 10个月对3.3个月,P<0.001)。与TKI初始治疗失败患者相比,之前未接受TKI治疗的LM患者生存期更长(12.2个月对9.2个月;P=0.016)。与未接受WBRT患者相比,WBRT的患者并未显示出生存优势(9.3个月对 8.1个月;P=0.448),且WBRT与TKI联合应用与TKI单用相比,未显著延长生存期(9.7个月对10.1个月;P=0.778)。LM后化疗与生存期延长相关,接受化疗者生存期为21个月,而未接受化疗者生存期为8.7个月(P=0.001)。

总体来说,能显著影响LM生存期的两个因素分别是TKI(P<0.001, HR=0.218)和化疗(P<0.001, HR=0.206)。

  • 作者认为:

“尽管仍有局限,此项研究显示的LM后OS期比既往报道更长,且携带EGFR突变基因的NSCLC患者LM更为常见。EGFR TKI是EGFR突变LM患者的最佳治疗策略,尤其是针对TIK初治患者。然而,无论是否联合EGFR TKI,此项研究并不支持积极的全脑放疗。

另外,我们启动的比较EGFR TKI埃可替尼和全脑放疗的头对头前瞻性随机对照研究BRAIN,也将在12月份的世界肺癌大会(WCLC)上公布结果。”

本文参考:Leptomeningeal Metastases Are More Common inNSCLC Patients Harboring EGFR Mutationsand Respond Positively to TKI Therapy.  Written by: Jacinta Wiens, PhD 

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level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160817/IMG57B3C3F6DC2FD8753.jpg, createdBy=81321934679, createdName=1e0d99ddm02(暂无匿称), createdTime=Sun Aug 21 16:33:00 CST 2016, time=2016-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384157, encodeId=d31e138415ee5, content=<a href='/topic/show?id=14bb1e503a0' target=_blank style='color:#2F92EE;'>#TKI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17503, encryptionId=14bb1e503a0, topicName=TKI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b73f484, createdName=lsj628, createdTime=Sat Aug 20 12:16:00 CST 2016, time=2016-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534287, encodeId=9c3e153428ecc, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Sat Aug 20 12:16:00 CST 2016, time=2016-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101220, encodeId=59c1101220b8, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Fri Aug 19 23:03:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101172, encodeId=87df1011e20e, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Fri Aug 19 22:57:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-31 ghy

    不错,

    0

  4. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101172, encodeId=87df1011e20e, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Fri Aug 19 22:57:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-26 李东泽

    这篇资讯写的真好,带给我们新知识,启发新思维,不论是科研还是临床工作都有很大的帮助。。。

    0

  5. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101172, encodeId=87df1011e20e, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Fri Aug 19 22:57:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-26 李东泽

    这篇资讯写的真好,带给我们新知识,启发新思维,不论是科研还是临床工作都有很大的帮助。。。

    0

  6. 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href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Sat Aug 20 12:16:00 CST 2016, time=2016-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101220, encodeId=59c1101220b8, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Fri Aug 19 23:03:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101172, encodeId=87df1011e20e, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Fri Aug 19 22:57:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-21 1e0d99ddm02(暂无匿称)

    学习了!!?

    0

  7. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101172, encodeId=87df1011e20e, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Fri Aug 19 22:57:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-20 lsj628
  8. 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    2016-08-20 liuyiping
  9. 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    2016-08-19 136****0753赵

    值得学习

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    2016-08-19 136****0753赵

    值得学习

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