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CLIN CHEM:黑色素瘤患者血浆中循环肿瘤DNA的液体分析用于伴随诊断和BRAF抑制剂治疗的监测

2018-05-22 MedSci MedSci原创

目前对于确定BRAF靶向治疗转移性黑色素瘤患者资格的标准是基于组织的BRAF突变检测。由于患者很少进行再次手术,通过实时全面评估肿瘤突变状态,从而在血液中检测可能是有利的,这也代表监测BRAF治疗的无创生物标志物。 本研究总共有634例I〜IV期黑素瘤患者被纳入到2个中心,并前瞻性收集1406例血浆标本。患者被分配到3个独立的研究队列中:作为伴随诊断的一部分的用于评估循环肿瘤DNA(ctDN

目前对于确定BRAF靶向治疗转移性黑色素瘤患者资格的标准是基于组织的BRAF突变检测。由于患者很少进行再次手术,通过实时全面评估肿瘤突变状态,从而在血液中检测可能是有利的,这也代表监测BRAF治疗的无创生物标志物。

本研究总共有634IIV期黑素瘤患者被纳入到2个中心,并前瞻性收集1406例血浆标本。患者被分配到3个独立的研究队列中:作为伴随诊断的一部分的用于评估循环肿瘤DNActDNA)的研究1,用于低肿瘤负荷和随访的患者的ctDNA的评估的研究2以及用于监测对BRAF抑制剂(BRAFi)或丝裂原活化蛋白激酶抑制剂治疗抗性的研究队列3

研究发现,总体而言,血浆和组织检测结果之间高度一致,分别为90.9%(研究1)和90.1%(研究2)。值得注意的是,在某些情况下,与BRAFi无应答(n = 3)或继发性BRAF突变恶性肿瘤(n = 5)相关的结果存在差异。重要的是,ctDNA结果与95.7%的疾病临床过程和治疗反应相关。值得注意的是,BRAF突变ctDNA 的检测先于实体瘤反应评估标准评估的复发,并且比血清S100和乳酸脱氢酶更具特异性。

研究表明基于血液的检测与基于标准组织的BRAF突变检测相当。重要的是,即使对于早期患者,基于血液的BRAF检测也与临床病程相关,并且可用于预测BRAFi治疗下放射成像前对治疗,复发和耐药的反应,从而显著改善患者治疗。

 

原始出处:

Verena Haselmann, Christoffer Gebhardt, Ingrid Brechtel. et.al. Liquid Profiling of Circulating Tumor DNA in Plasma of Melanoma Patients for Companion Diagnostics and Monitoring of BRAF Inhibitor Therapy.

本文系梅斯医学(MedSci)原创编译整理,转载需授权!


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    2018-08-02 sunylz
  4. [GetPortalCommentsPageByObjectIdResponse(id=1936825, encodeId=d58b193682559, content=<a href='/topic/show?id=0c3f1509582' target=_blank style='color:#2F92EE;'>#RAF抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15095, encryptionId=0c3f1509582, topicName=RAF抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ca772500164, createdName=ms1490123962508630, createdTime=Fri Aug 31 02:27:00 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956434, encodeId=ab60195643404, content=<a href='/topic/show?id=326f2610414' target=_blank style='color:#2F92EE;'>#伴随诊断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26104, encryptionId=326f2610414, topicName=伴随诊断)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/fa8I6JticHgohY5FSGE98I1F4gpCjrpl2nbN6jZJY6JEqAjUibjItOA9AsgbBwTuBzAPbU5Tl8DxfemWUFFzBOYw/132, createdBy=24c12500054, createdName=ms2186806800017884, createdTime=Mon Oct 01 13:27:00 CST 2018, time=2018-10-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680530, encodeId=00611680530dd, content=<a href='/topic/show?id=9e5c86e0712' target=_blank style='color:#2F92EE;'>#色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86707, encryptionId=9e5c86e0712, topicName=色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=343027846633, createdName=sunylz, createdTime=Thu Aug 02 19:27:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851718, encodeId=0d771851e182c, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Feb 04 01:27:00 CST 2019, time=2019-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1354990, encodeId=8498135499093, content=<a href='/topic/show?id=6de63659ed' target=_blank style='color:#2F92EE;'>#BRAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3659, encryptionId=6de63659ed, topicName=BRAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484860, encodeId=fa17148486055, content=<a href='/topic/show?id=35a050454a5' target=_blank style='color:#2F92EE;'>#循环肿瘤DNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50454, encryptionId=35a050454a5, topicName=循环肿瘤DNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ac107986109, createdName=ms1948154235210413, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1530188, encodeId=45b01530188e2, content=<a href='/topic/show?id=6b4d3668c3' target=_blank style='color:#2F92EE;'>#BRAF抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3668, encryptionId=6b4d3668c3, topicName=BRAF抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=292d12051665, createdName=hjwang83, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558901, encodeId=3eb11558901e8, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564910, encodeId=b19f15649101e, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=317771, encodeId=f67131e77161, content=了解一下谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed May 23 07:33:35 CST 2018, time=2018-05-23, status=1, ipAttribution=)]
    2019-02-04 jklm09
  5. [GetPortalCommentsPageByObjectIdResponse(id=1936825, encodeId=d58b193682559, content=<a href='/topic/show?id=0c3f1509582' target=_blank style='color:#2F92EE;'>#RAF抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15095, encryptionId=0c3f1509582, topicName=RAF抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ca772500164, createdName=ms1490123962508630, createdTime=Fri Aug 31 02:27:00 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956434, encodeId=ab60195643404, content=<a href='/topic/show?id=326f2610414' target=_blank style='color:#2F92EE;'>#伴随诊断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26104, encryptionId=326f2610414, topicName=伴随诊断)], attachment=null, authenticateStatus=null, 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style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Feb 04 01:27:00 CST 2019, time=2019-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1354990, encodeId=8498135499093, content=<a href='/topic/show?id=6de63659ed' target=_blank style='color:#2F92EE;'>#BRAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3659, encryptionId=6de63659ed, topicName=BRAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484860, encodeId=fa17148486055, content=<a href='/topic/show?id=35a050454a5' target=_blank style='color:#2F92EE;'>#循环肿瘤DNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50454, encryptionId=35a050454a5, topicName=循环肿瘤DNA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ac107986109, createdName=ms1948154235210413, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1530188, encodeId=45b01530188e2, content=<a href='/topic/show?id=6b4d3668c3' target=_blank style='color:#2F92EE;'>#BRAF抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3668, encryptionId=6b4d3668c3, topicName=BRAF抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=292d12051665, createdName=hjwang83, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1558901, encodeId=3eb11558901e8, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=82, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564910, encodeId=b19f15649101e, content=<a href='/topic/show?id=e27610332666' target=_blank style='color:#2F92EE;'>#黑色素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=317771, encodeId=f67131e77161, content=了解一下谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed May 23 07:33:35 CST 2018, time=2018-05-23, status=1, ipAttribution=)]
    2018-05-24 zhaojie88
  6. [GetPortalCommentsPageByObjectIdResponse(id=1936825, encodeId=d58b193682559, content=<a href='/topic/show?id=0c3f1509582' target=_blank style='color:#2F92EE;'>#RAF抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15095, encryptionId=0c3f1509582, topicName=RAF抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ca772500164, createdName=ms1490123962508630, createdTime=Fri Aug 31 02:27:00 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956434, encodeId=ab60195643404, content=<a href='/topic/show?id=326f2610414' target=_blank style='color:#2F92EE;'>#伴随诊断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26104, encryptionId=326f2610414, topicName=伴随诊断)], attachment=null, authenticateStatus=null, 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style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Feb 04 01:27:00 CST 2019, time=2019-02-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1354990, encodeId=8498135499093, content=<a href='/topic/show?id=6de63659ed' target=_blank style='color:#2F92EE;'>#BRAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3659, encryptionId=6de63659ed, topicName=BRAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), 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topicId=null, topicList=[TopicDto(id=103326, encryptionId=e27610332666, topicName=黑色素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=150614999302, createdName=cqlidoudou, createdTime=Thu May 24 06:27:00 CST 2018, time=2018-05-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=317771, encodeId=f67131e77161, content=了解一下谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Wed May 23 07:33:35 CST 2018, time=2018-05-23, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1936825, encodeId=d58b193682559, content=<a href='/topic/show?id=0c3f1509582' target=_blank style='color:#2F92EE;'>#RAF抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15095, encryptionId=0c3f1509582, topicName=RAF抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ca772500164, createdName=ms1490123962508630, createdTime=Fri Aug 31 02:27:00 CST 2018, time=2018-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1956434, encodeId=ab60195643404, content=<a href='/topic/show?id=326f2610414' target=_blank style='color:#2F92EE;'>#伴随诊断#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=26104, encryptionId=326f2610414, topicName=伴随诊断)], attachment=null, authenticateStatus=null, 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    2018-05-23 kafei

    了解一下谢谢

    0

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