病例:特瑞普利单抗联合化疗新辅助治疗获PR,初始手术困难的食管鳞癌患者成功施行根治术

2019-12-06 佚名 肿瘤资讯

免疫治疗在食管癌中进展迅速,已在晚期食管癌患者的二线及以上治疗中表现出较化疗更优的生存结果。其在食管癌一线治疗中的研究也有多项在进行中。不仅如此,鉴于免疫治疗的治疗潜力,其与化疗、化放疗联合用于可切除食管癌新辅助治疗的研究也取得了初步成果,为局部晚期的患者带来了获益可能。本文介绍的这例食管癌患者,初始手术切除有困难,经PD-1单抗特瑞普利单抗联合化疗新辅助治疗后,原发灶明显缩小,得以成功实施根治性

免疫治疗在食管癌中进展迅速,已在晚期食管癌患者的二线及以上治疗中表现出较化疗更优的生存结果。其在食管癌一线治疗中的研究也有多项在进行中。不仅如此,鉴于免疫治疗的治疗潜力,其与化疗、化放疗联合用于可切除食管癌新辅助治疗的研究也取得了初步成果,为局部晚期的患者带来了获益可能。本文介绍的这例食管癌患者,初始手术切除有困难,经PD-1单抗特瑞普利单抗联合化疗新辅助治疗后,原发灶明显缩小,得以成功实施根治性手术。

病例介绍

基本情况

患者男,64岁,2019年4月因“吞咽困难”就诊于外院,镜检查:距门齿36~41cm右侧壁见一菜花样肿物,病理活检示食管鳞癌。

入院后检查及治疗

随后来我院就诊,胸腹增强CT检查显示T6~T10水平食管壁增厚、管腔狭窄,病灶与周围组织关系紧密,切除困难,遂行“顺铂+紫杉醇+特瑞普利单抗”三药新辅助治疗2个周期,复查见原发病灶明显缩小,疗效评价:部分缓解(PR)。

4周后完善相关辅助检查未见手术禁忌,在胸腹腔镜联合下行食管下段鳞癌切除+管状代食管颈部吻合术+淋巴结清扫。术后病理(免疫组化):CK5/6(部分+)、CK7(部分+)、Ki67(+,30%),食管鳞状细胞癌;淋巴结见癌转移(食管旁淋巴结1/16,右喉返神经旁淋巴结0/4,左喉返神经旁淋巴结0/10,第4组淋巴结0/6,第5组淋巴结0/4,左侧第10组淋巴结1/1,右侧第10组淋巴结0/4,胃旁淋巴结0/27),术后诊断:食管下段鳞癌(pT3N1M0,ⅢB期)。术后3天拔除胸管,5天进食,7天出院。

戴天阳 主任医师 教授,西南医科大学附属医院胸外科主任,中国医师协会规培住院医生基地委员,中国医师协会胸外科分会委员,中国医促会胸外科分会委员,中国医研会胸外科分会委员,海峡两岸胸外科协会委员,四川省胸外科医师协会副组长,四川省食管癌专委会副主任委员,四川省食管良性疾病专委员副主任委员,四川省胸心血管专委会常委。

专家点评

目前,免疫治疗在食管癌中的研究如火如荼。基于KEYNOTE-181研究的结果,PD-1单抗帕博利珠单抗单药已获FDA批准用于PD-L1阳性(CPS≥10)食管鳞癌患者的二线治疗。ATTRACTION-3研究中,纳武利尤单抗对比化疗二线治疗食管鳞癌亦显着改善患者OS,NCCN指南已经推荐可成为新的二线治疗标准。

特瑞普利单抗在食管癌中的研究也在进行中,该药是第一个获批上市的中国自主生产的抗PD-1受体的全人源单克隆抗体,通过封闭T淋巴细胞的PD-1,阻断其与肿瘤细胞表面的PD-L1结合,解除肿瘤细胞对免疫细胞的免疫抑制,促使免疫细胞重新发挥抗肿瘤作用。一项比较特瑞普利单抗联合标准化疗(紫杉醇+顺铂)与安慰剂联合标准化疗在一线治疗晚期或者转移性食管鳞癌的Ⅲ期、随机、双盲、安慰剂对照、多中心临床研究正在进行(JS001-021-Ⅲ-ESCC),我们科室是分中心之一。

对于食管癌的新辅助治疗,目前也有多项研究正在进行中。2019年ASCO大会上公布了Ⅱ期PERFECT研究的结果,该研究以PD-L1单抗阿替利珠单抗与化疗(化疗方案同经典的食管癌新辅助化放疗研究CROSS,即卡铂+紫杉醇)联合,用于可切除食管腺癌的新辅助治疗,共纳入39例患者,在已接受手术的23例患者中,9例达病理完全缓解(pCR),pCR率达39%,高于CROSS研究中食管腺癌患者中23%的pCR率。且免疫联合化放疗的毒性可管理。虽然研究结果有待更大型的随机临床研究进一步确认,但免疫联合治疗可能是治疗可切除性局部晚期食管鳞癌的未来的一个优选方案。

该患者新辅助治疗前食管病灶大、与周围组织界限不清楚,手术切除难度大,且难以做到R0切除,属于局部晚期。因此先行2个周期的新辅助治疗,再评估是否可手术治疗。研究显示,对于可切除的食管癌,单纯的新辅助化疗效果不佳[1];结合我科正在进行的临床试验,制定了“顺铂+紫杉醇+特瑞普利单抗”的三药新辅助治疗方案。

从作用机制来看,化疗与免疫联合有协同抗肿瘤作用:化疗药物对免疫系统具有双重调节作用,可在肿瘤微环境、肿瘤细胞、机体免疫系统等方面促进肿瘤免疫应答;化疗药物可以增强肿瘤细胞抗原性(铂类、紫杉醇、吉西他滨)、提高肿瘤细胞的免疫原性、增强肿瘤细胞对免疫效应细胞的敏感性(铂类、紫杉醇),还可以消除免疫抑制性细胞(紫杉醇、吉西他滨、顺铂)、促进抗原交叉递呈和抗肿瘤免疫应答。免疫治疗可通过增强抗肿瘤的免疫反应提高患者对化疗的敏感性。两者相辅相成,并且多项研究表明,化疗联合免疫治疗可提高肿瘤客观缓解率(ORR),延长患者生存期。

该患者在应用化疗联合特瑞普利单抗2个周期后,复查见食管病灶明显缩小,疗效评估达PR,最终得以成功实施根治性手术。免疫治疗不仅在晚期食管癌中的疗效获确切证实,其在新辅助治疗中的作用也大有前景,值得在临床研究和实践中进一步探索。

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  4. 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  5. 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  6. 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createdBy=745a7977375, createdName=1696533704_45270456, createdTime=Sun Dec 08 13:15:00 CST 2019, time=2019-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1586166, encodeId=045e15861669f, content=<a href='/topic/show?id=38f8622191b' target=_blank style='color:#2F92EE;'>#根治#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=62219, encryptionId=38f8622191b, topicName=根治)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=26d917348678, createdName=jeanqiuqiu, createdTime=Sun Dec 08 13:15:00 CST 2019, time=2019-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376685, encodeId=81a93e668567, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bbc11488193, createdName=thm112988, createdTime=Sun Dec 08 07:20:02 CST 2019, time=2019-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376660, encodeId=72583e66603c, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sat Dec 07 10:50:09 CST 2019, time=2019-12-07, status=1, ipAttribution=)]
    2019-12-08 zhouqu_8
  7. 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beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101059, encryptionId=0e311010591a, topicName=食管)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Dec 08 13:15:00 CST 2019, time=2019-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484671, encodeId=267c14846e106, content=<a href='/topic/show?id=3502102944e7' target=_blank style='color:#2F92EE;'>#鳞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102944, encryptionId=3502102944e7, topicName=鳞癌)], attachment=null, authenticateStatus=null, createdAvatar=Bioon/avatar/20171006/a73877485ccdf6add82293e671bebe21.jpg, 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createdBy=bbc11488193, createdName=thm112988, createdTime=Sun Dec 08 07:20:02 CST 2019, time=2019-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376660, encodeId=72583e66603c, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sat Dec 07 10:50:09 CST 2019, time=2019-12-07, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=2027417, encodeId=1012202e41759, content=<a href='/topic/show?id=48b368e28ea' target=_blank style='color:#2F92EE;'>#瑞普利单抗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68728, encryptionId=48b368e28ea, topicName=瑞普利单抗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=da20314, createdName=lfcmxl, createdTime=Sat Sep 19 22:15:00 CST 2020, time=2020-09-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1678617, encodeId=df0b16e861749, content=<a href='/topic/show?id=110c5869153' target=_blank style='color:#2F92EE;'>#新辅助#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58691, encryptionId=110c5869153, topicName=新辅助)], attachment=null, authenticateStatus=null, createdAvatar=null, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101059, encryptionId=0e311010591a, topicName=食管)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sun Dec 08 13:15:00 CST 2019, time=2019-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484671, encodeId=267c14846e106, content=<a href='/topic/show?id=3502102944e7' target=_blank style='color:#2F92EE;'>#鳞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102944, encryptionId=3502102944e7, topicName=鳞癌)], attachment=null, authenticateStatus=null, createdAvatar=Bioon/avatar/20171006/a73877485ccdf6add82293e671bebe21.jpg, 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createdBy=bbc11488193, createdName=thm112988, createdTime=Sun Dec 08 07:20:02 CST 2019, time=2019-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376660, encodeId=72583e66603c, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sat Dec 07 10:50:09 CST 2019, time=2019-12-07, status=1, ipAttribution=)]
    2019-12-08 jeanqiuqiu
  9. 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createdBy=bbc11488193, createdName=thm112988, createdTime=Sun Dec 08 07:20:02 CST 2019, time=2019-12-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=376660, encodeId=72583e66603c, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sat Dec 07 10:50:09 CST 2019, time=2019-12-07, status=1, ipAttribution=)]
    2019-12-08 thm112988

    0

  10. 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    2019-12-07 1ddf0692m34(暂无匿称)

    学习了,谢谢分享

    0

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