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患有ALK驱动的复发性或阻断性神经母细胞瘤的患者对洛拉提尼布的长期反应,通过循环瘤DNA分析监测

Torben Ek^1,2, Raghda R Ibrahim^2,3, Hartmut Vogt⁴

¹Children's Cancer Centre, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, Sweden.

Cancer research communications

|August 23, 2024

概括

针对性循环瘤DNA (ctDNA) 分析显示,它有望指导ALK突变的神经母细胞瘤患者的治疗. 这种方法有助于监测对洛拉提尼布的反应,并比标准方法更早地检测复发.

科学领域:

在瘤学瘤学.
遗传学是一个遗传学.
分子生物学分子生物学

背景情况:

亚纳普拉斯性淋巴瘤激酶 (ALK) 驱动的神经母细胞瘤可以对氨酸激酶抑制剂产生耐药性.
目前用于检测神经母细胞瘤残留疾病的方法的灵敏度有限.
针对性循环瘤DNA (ctDNA) 分析为敏感的疾病检测提供了潜在的解决方案.

研究的目的:

评估洛拉提尼布单一治疗在复发或耐药ALK驱动神经母细胞瘤患者中的疗效.
评估针对性ctDNA分析对指导这些患者治疗决策的有用性.
为了确定ctDNA分析是否可以实现复发的早期检测.

主要方法:

一个由5名患有复发性/耐药性ALK驱动神经母细胞瘤的患者组成的全国队列接受了洛拉提尼布单一治疗.
开发了一个敏感的测序面板,用于检测ctDNA中的ALK突变.
用超深度测序对血样本进行了纵向ctDNA分析.

主要成果:

所有四名患有ALK p.R1275Q突变的患者都表现出较大的反应,存活了35-61个月.
第五个患有ALK p.F1174L的患者有部分反应,但在10个月后复发.
ctDNA水平与临床反应相关,随着治疗而下降,并在临床复发之前增加.
在8个月的洛拉提尼布治疗后,在一名患者的ctDNA中检测到一种新的HRAS突变.

结论:

洛拉提尼布单独治疗可以在一些复发/耐药高风险神经母细胞瘤患者中引起持久反应.
针对性ctDNA分析是有效的监测治疗反应,并使早期检测ALK驱动的神经母细胞瘤的复发.
ctDNA分析可以指导治疗决策,即使疾病不能通过标准方法检测到.

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