Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Hematologic Disease Laboratory, Hematology Center, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Mol Cancer Ther. 2021 Jul;20(7):1316-1323. doi: 10.1158/1535-7163.MCT-20-1075. Epub 2021 Apr 20.
The aim of this study was to investigate the prognostic significance of BRAF in cell-free (cf) DNA (cfBRAF) and lesion tissues (ltBRAF) in pediatric Langerhans cell histiocytosis (LCH). This study included a total of 140 patients with successfully detected cfBRAF and ltBRAF at diagnosis. Treatment response at week 6 was correlated with both cfBRAF and ltBRAF Moreover, the patients with positive cfBRAF had a much lower 3-year progression-free survival (PFS) rate and a higher progression/reactivation rate than those with negative cfBRAF (47.1% ± 7.6% vs. 78.4% ± 5.1%, < 0.0001; 44.6% vs. 19.0%, = 0.001, respectively). However, no significant difference was found in the 3-year PFS rate or progression/reactivation rate between patients with positive and negative ltBRAF ( = 0.348 and 0.596, respectively). In addition, after patients were divided into group A (both cfBRAF and ltBRAF positive, = 56), group B (ltBRAF positive and cfBRAF negative, = 28), and group C (both cfBRAF and ltBRAF negative, = 56), there was a significant difference in the 3-year PFS rate and progression/reactivation rate among the three groups (47.1% ± 7.6%, 92.9% ± 6.1%, and 72.2% ± 6.1%, < 0.001; 44.6%, 3.6%, and 26.8%, < 0.001, respectively). In the multivariate analysis, cfBRAF and age at diagnosis remained independent prognostic factors for 3-year PFS in childhood LCH. Therefore, cfBRAF was more closely associated with important clinical characteristics, treatment response at week 6, and prognosis than ltBRAF.
本研究旨在探讨 BRAF 在儿童朗格汉斯细胞组织细胞增生症（LCH）的游离细胞（cf）DNA（cfBRAF）和病变组织（ltBRAF）中的预后意义。本研究共纳入 140 例成功检测到诊断时 cfBRAF 和 ltBRAF 的患者。第 6 周的治疗反应与 cfBRAF 和 ltBRAF 均相关。此外，cfBRAF 阳性患者的 3 年无进展生存率（PFS）明显低于 cfBRAF 阴性患者（47.1%±7.6%比 78.4%±5.1%，<0.0001；44.6%比 19.0%，=0.001）。然而，ltBRAF 阳性和阴性患者的 3 年 PFS 率或进展/复发率无显著差异（=0.348 和 0.596）。此外，将患者分为 A 组（cfBRAF 和 ltBRAF 均阳性，=56）、B 组（ltBRAF 阳性而 cfBRAF 阴性，=28）和 C 组（cfBRAF 和 ltBRAF 均阴性，=56）后，三组患者的 3 年 PFS 率和进展/复发率有显著差异（47.1%±7.6%、92.9%±6.1%和 72.2%±6.1%，<0.001；44.6%、3.6%和 26.8%，<0.001）。多变量分析显示，cfBRAF 和诊断时的年龄是儿童 LCH 3 年 PFS 的独立预后因素。因此，cfBRAF 比 ltBRAF 更密切地与重要的临床特征、第 6 周的治疗反应和预后相关。
