马文斌:老年胶质母细胞瘤患者分子遗传学特点及治疗前评估

2018-05-04 王雅宁 高晶 朱鸣雷 管梅 宁晓红 王裕 马文斌(中国医学科学院 北京协和医院神经外科) 中华医学信息导报

胶质母细胞瘤(GBM)是一种恶性程度极高,也是成年人中最常见的原发性恶性脑肿瘤,其发病率会随着年龄的增长而增加,大于65岁的患者发病率为年轻人群的2.63倍。另外,老年GBM患者的预后更差,而目前对于老年GBM的临床及基础研究远不能满足老龄化社会对医疗管理人员的要求。


马文斌

胶质母细胞瘤(GBM)是一种恶性程度极高,也是成年人中最常见的原发性恶性脑肿瘤,其发病率会随着年龄的增长而增加,大于65岁的患者发病率为年轻人群的2.63倍。另外,老年GBM患者的预后更差,而目前对于老年GBM的临床及基础研究远不能满足老龄化社会对医疗管理人员的要求。本文对老年GBM患者的分子遗传学特点进行归纳并对该类患者治疗前评估重要性进行叙述,以期制订出更加适合老年GBM患者的治疗决策与方案

老年GBM患者分子遗传学特点

就老年GBM而言,其分子遗传学特点为:(1)基因组不稳定,与小于45岁GBM患者相比,大于70岁GBM患者ATRX、BRAF、IDH、TP53突变率明显下降,而PTEN基因突变比率明显增加;(2)表观遗传学改变,多个研究表明,衰老相关的表观遗传学标签与GBM患者生存相关;(3)老年GBM的分子亚型,具有较好预后的老年GBM分子亚型为具有高表达EGFR者;(4)胶质瘤随着年龄的增加,以14个衰老相关基因表达为主构成的衰老评分逐步增高。

老年GBM肿瘤治疗前评估方向及量表选择

目前针对老年GBM患者的治疗方案主要包括手术切除,放疗以及替莫唑胺为主的化疗和分子靶向治疗。现有的几项临床试验均显示,手术切除可以使老年GBM患者生存获益。但随着年龄的增加,手术的风险也急剧增加。目前学术界认为,进行综合老年状态评估后,评价较好者进行手术切除具有良好的安全性和临床获益。同理, 开展老年GBM放疗、化疗也需要有综合评估。

治疗评估主要可集中在六个方面,即:生命质量评估、合并症评估、认知能力评价、衰弱程度评价、营养评估及其他方面评估。而评估的形式为量表。在六个评估方向上,生命质量是对患者一般情况的概括,是总体评价的依据。合并症和认知能力经文献报道,均为老年胶质瘤患者预后(总生存期和无进展生存期)的独立影响因素。衰弱程度与手术耐受与否相关,并会间接影响老年GBM患者的生存期,且文献报道衰弱程度较高的老年GBM患者住院时间更长,在院期间能够耐受的侵入性干预更少,术后出现的并发症更多。据报道,44%的老年癌症患者存在严重的营养不良,患者的营养程度不仅影响患者住院时间,而且也能作为患者预后的预测因子。其他方面,包括血红蛋白以及白蛋白等指标以及多样药物交互作用及不良反应。

针对上述6个评估方向,多数学者认可的量表如下:(1)生命质量评估推荐日常生活能力量表、癌症患者生命质量测定量表;(2)合并症评估推荐查尔森合并症指数;(3)认知能力及精神情绪评估推荐简易精神状态评价量表、蒙特利尔认知评估量表以及医院焦虑抑郁量表;(4)衰弱程度评估推荐衰弱筛查量表及Karnofsky功能状态评分标准;(5)营养状态评估推荐简易营养评价量表;(6)其他方面评估,应考虑评估老年患者包括血红蛋白、白蛋白等指标以及伴随疾病所服用药物的副作用和这些药物与治疗胶质瘤的化疗、靶向治疗药物的相互作用等。

小结

目前,中国老龄化日益严重,加之GBM患者多为老年人,故针对老年GBM分子遗传学特点建立治疗决策系统及基于分子病理的个体化治疗方案具有迫切性。应以神经肿瘤专家为主,组成与神经内科、肿瘤内科及老年医学科等专家联合的MDT团队,共同制定一套针对老年GBM患者治疗前综合评估的方法,以保证顺利完成老年GBM患者的治疗,同时还能优化治疗决策及治疗方案,从而达到精准治疗、个体化治疗的目的。

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encryptionId=05e29508559, topicName=遗传学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6e7948, createdName=李研东, createdTime=Fri Jul 27 22:59:00 CST 2018, time=2018-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313577, encodeId=83383135e7f2, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Wed May 09 22:09:19 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313362, encodeId=a45131336274, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, 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objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Tue May 08 18:52:24 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=312947, encodeId=962c31294e31, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Mon May 07 22:05:56 CST 2018, time=2018-05-07, status=1, ipAttribution=), 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    2018-08-17 一一一多

    厉害,从基础到临床

    0

  4. 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    2018-05-09 1e145228m78(暂无匿称)

    学习了.谢谢作者分享!

    0

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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Wed May 09 06:19:46 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313269, encodeId=56f731326953, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Tue May 08 22:51:53 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313210, encodeId=7019313210a4, content=一起学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Tue May 08 18:52:24 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=312947, encodeId=962c31294e31, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Mon May 07 22:05:56 CST 2018, time=2018-05-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=312734, encodeId=9aa9312e340b, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Mon May 07 06:35:12 CST 2018, time=2018-05-07, status=1, ipAttribution=)]
    2018-05-09 wzb521zf

    一起学习学习

    0

  7. 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createdBy=a691420, createdName=30397604, createdTime=Mon Aug 13 04:59:00 CST 2018, time=2018-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=339155, encodeId=bb7e33915591, content=厉害,从基础到临床, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/eiadcQaiaZ4fUvicZKEbibPBA2otZ0yzMeAVET5icsaS77W0Tvo3ibFMibzxTVRPsg62xJu0GicwBCvAlPMyu7TB6j86ug/132, createdBy=d64c1981665, createdName=一一一多, createdTime=Fri Aug 17 17:15:20 CST 2018, time=2018-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1843955, encodeId=6157184395596, content=<a href='/topic/show?id=05e29508559' target=_blank style='color:#2F92EE;'>#遗传学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95085, encryptionId=05e29508559, topicName=遗传学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6e7948, createdName=李研东, createdTime=Fri Jul 27 22:59:00 CST 2018, time=2018-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313577, encodeId=83383135e7f2, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Wed May 09 22:09:19 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313362, encodeId=a45131336274, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, 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    2018-05-08 1e145228m78(暂无匿称)

    学习了.谢谢作者分享!

    0

  8. 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encryptionId=05e29508559, topicName=遗传学)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6e7948, createdName=李研东, createdTime=Fri Jul 27 22:59:00 CST 2018, time=2018-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313577, encodeId=83383135e7f2, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Wed May 09 22:09:19 CST 2018, time=2018-05-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=313362, encodeId=a45131336274, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, 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objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Tue May 08 18:52:24 CST 2018, time=2018-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=312947, encodeId=962c31294e31, content=学习了.谢谢作者分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xJXLtMtt5B40XXuPjn9xn1rBhrM6fHLkX1hI86ZoWoPJkgDkZuJNKkBfBHOcRd1fAdezg7JlHNOokohdAp3WkI/0, createdBy=32c81964262, createdName=1e145228m78(暂无匿称), createdTime=Mon May 07 22:05:56 CST 2018, time=2018-05-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=312734, encodeId=9aa9312e340b, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Mon May 07 06:35:12 CST 2018, time=2018-05-07, status=1, ipAttribution=)]
    2018-05-08 wzb521zf

    一起学习学习学习

    0

  9. 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    2018-05-07 1e145228m78(暂无匿称)

    学习了.谢谢作者分享!

    0

  10. 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    2018-05-07 wzb521zf

    一起学习学习

    0

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