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NEJM:转移性黑色素瘤治疗后的一个罕见现象

2012-03-10 MedSci MedSci原创

 在癌症治疗后发生了一个罕见现象,病人局部放疗后出现系统性反应,这种情况被称为远端效应(abscopal effect),发生在一个患转移性黑色素瘤的40岁妇女身上,该妇女接受Ipilimumab(Yervoy,施贵宝)的免疫治疗。本文发表在3月8日的新英格兰杂志上。 病人是一位一直在工作的单身母亲,在放疗期间一直使用Ipilimumab进行维持治疗,治疗医生为纪念斯隆 - 凯特

 在癌症治疗后发生了一个罕见现象,病人局部放疗后出现系统性反应,这种情况被称为远端效应(abscopal effect),发生在一个患转移性黑色素瘤的40岁妇女身上,该妇女接受Ipilimumab(Yervoy,施贵宝)的免疫治疗。本文发表在3月8日的新英格兰杂志上。


病人是一位一直在工作的单身母亲,在放疗期间一直使用Ipilimumab进行维持治疗,治疗医生为纪念斯隆 - 凯特琳癌症中心的Jedd Wolchok博士。该病人在CT检查时发现右侧肺门淋巴结肿大,沿脊柱有一个胸膜肿瘤,之后在2009年9月进入Ipilimumab的II期临床研究。使用Ipilimumab 12周后,病人病情稳定,但是胸膜体积略有扩大,因此,她进行维持治疗,每12周服用一个剂量。

2010年底,一直进行维持治疗的病人病情进展,出现新的脾脏病变和胸膜体积的持续增大,最终引起疼痛。为了缓解疼痛,开始进行姑息性放疗。在2010年12月放疗期间,Wolchok博士有了一个想法,通过治疗可能会诱发远端效应。在动物实验中发现了很多远端效应的报道,但是在人群中是非常罕见的,在黑色素瘤中可能有一例。


放疗后,该病人接受多一次剂量的Ipilimumab,4个月后,在2011年4月,照射的肿瘤明显缩小,这是意料之中的。令人吃惊的是,放疗部位之外的远端肿瘤也出现缩小的现象。在2011年10月CT检查发现,放疗10个月后,病人疾病达到最小程度。


Wolchok博士起初认为这个病人的结局是Ipilimumab的延迟效应。Ipilimumab治疗18~20周的延迟效应是常见的,但是,在研究组看来,开始使用Ipilimumab和疾病反应之间的19个月间隔,其中插入了放疗,很有可能是因为远端效应造成的。

治疗小组还检测了病人的血液,测定免疫反应相关的指标。他们观察到肿瘤指向的抗体水平和免疫细胞数量的改变。

这个治疗结局对病人无疑是一个好消息,此外,远端效应的产生对于其他服用Ipilimumab的病人和癌症研究也是一个好消息。该病例提示应追求新的治疗途径。前瞻性验证这种方法的临床试验目前有前列腺癌(NCT00861614)和黑色素瘤(NCT01449279)。

同时,开出Ipilimumab处方的医生可以尝试对一些病人同时实行放疗,例如那些需要缓解症状的病人,可能通过放疗提高Ipilimumab的治疗指数。

Wolchok博士推测Ipilimumab和放疗可能协作的机制为:放疗可以造成DNA损伤,如果癌细胞死亡,碎片会激发免疫反应。因为碎片激发的免疫反应还不足,如果再通过其他方式进行激活,那么就会产生协同作用,这里就是通过Ipilimumab的免疫效应。

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    2012-04-28 sunylz
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    2012-03-12 syscxl
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