Liu Siying, Zhu Yongbing, Chen Yu, Wang Yaqin, Zhang Dedong, Zhang Jiasi, Wang Yao, Zhang Ai, Hu Qun, Liu Aiguo
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Children (Basel). 2024 Nov 27;11(12):1449. doi: 10.3390/children11121449.
The detection of mutations from circulating tumor DNA (ctDNA) represents a promising enrichment technique. In this retrospective study, the significance of ctDNA and imaging in Langerhans cell histiocytosis (LCH) monitoring was first examined, and the broader role of ctDNA in monitoring LCH was additionally explored.
First, data visualization and survival analysis models were used to generalize the concordance between cfBRAF molecular response and radiographic response on clinical outcomes. Next, the molecular response of cfBRAF was observed from a dynamic perspective. A comparative analysis was then conducted between cfBRAF and ltBRAF status, examining their relationship to clinical manifestations and prognosis of LCH.
Eventually, 119 participants were enrolled in this trial between 2019 and 2023. Progression-free survival (PFS) was significantly shorter in patients with both radiologic and cfDNA molecular progression (17.67 versus 24.67 months, < 0.05) compared to those without. A critical cfBRAF value of 0.03% has been determined for the first time. Both cfBRAF and ltBRAF mutations were associated with a higher proportion of children under 3 years of age, skin and spleen involvement, and a lower 3-year PFS rate. In contrast to ltBRAF, cfBRAF was linked to a higher proportion of risk organ invasion LCH (52% vs. 27.9%, < 0.05) and a better therapeutic response at the sixth week (24% vs. 4.7%, < 0.05). Furthermore, in patients with risk organ invasion-LCH and multisystem-LCH subtypes, cfBRAF was associated with a significantly lower 3-year PFS.
In summary, these findings enhanced and supplemented the implications of ctDNA and imaging analysis application in children with LCH.
从循环肿瘤DNA（ctDNA）中检测突变是一种很有前景的富集技术。在这项回顾性研究中，首先探讨了ctDNA和影像学在朗格汉斯细胞组织细胞增多症（LCH）监测中的意义，并进一步探索了ctDNA在LCH监测中的更广泛作用。
首先，使用数据可视化和生存分析模型来概括cfBRAF分子反应与影像学反应在临床结果上的一致性。接下来，从动态角度观察cfBRAF的分子反应。然后对cfBRAF和ltBRAF状态进行比较分析，研究它们与LCH临床表现和预后的关系。
最终，2019年至2023年间共有119名参与者纳入本试验。与无放射学和cfDNA分子进展的患者相比，有放射学和cfDNA分子进展的患者无进展生存期（PFS）显著缩短（17.67个月对24.67个月，P<0.05）。首次确定了0.03%的关键cfBRAF值。cfBRAF和ltBRAF突变均与3岁以下儿童、皮肤和脾脏受累比例较高以及3年PFS率较低相关。与ltBRAF相比，cfBRAF与风险器官侵犯性LCH的比例较高（52%对27.9%，P<0.05）以及第六周时更好的治疗反应相关（24%对4.7%，P<0.05）。此外，在风险器官侵犯性LCH和多系统LCH亚型患者中，cfBRAF与显著更低的3年PFS相关。
总之，这些发现强化并补充了ctDNA和影像学分析在LCH患儿中的应用意义。
