Background: Plexiform neurofibromas (PNs) are histologically benign peripheral nerve sheath tumors associated with neurofibromatosis type 1 (NF1) and often lead to significant morbidity due to growth. Management includes watchful waiting, surgery for partial debulking, and, since recently, systemic treatment with MEK inhibitors. However, due to the scarcity of natural history studies, our understanding of the natural progression of PNs to guide clinicians in deciding in whom and when to intervene is scarce. This study aims to describe the characteristics of NF1 patients with PNs and compare those at high risk for PN progression or experiencing significant morbidity from PN (complex PN) with NF1 patients with PNs of lower complexity. Methods: In this retrospective cohort study using clinical data from hospital records of NF1 patients with PNs seen at the Sophia Children’s Hospital in the Netherlands between 2012 and 2023, we assessed determinants of clinical phenotypes and PN characteristics predictive of outcomes, including PN complexity and the timing of intervention for PN. We assessed the outcomes using logistic regression analysis and Cox regression. Results: Ninety patients with a median age at last evaluation of 15.7 years and a median follow-up duration of 9.8 years were included. Out of 90 individuals with a benign PN, 37 developed plexiform neurofibroma morbidity during follow-up. Older age was (corrected for pathogenic NF1 variant and PN location) significantly associated with plexiform neurofibroma morbidity. Cox regression revealed that craniofacial and trunk PNs were associated with a higher intervention hazard compared to limb PNs. Conclusion: Our pilot multivariate approach identified older age and the location of the PN to be mostly associated with a higher chance of plexiform neurofibroma morbidity and higher intervention hazard. This may contribute to decisions regarding in whom and when to initiate treatment in NF1 patients with PNs.
背景：丛状神经纤维瘤（PNs）是组织学上良性的周围神经鞘肿瘤，与1型神经纤维瘤病（NF1）相关，常因生长导致显著发病率。管理策略包括观察等待、手术部分减瘤，以及近年来采用的MEK抑制剂全身治疗。然而，由于自然病程研究的缺乏，我们对PNs自然进展的理解有限，难以指导临床医生决定干预对象和时机。本研究旨在描述NF1伴PNs患者的特征，并将PN进展高风险或因此出现显著发病率（复杂PN）的患者与复杂性较低的NF1伴PNs患者进行比较。 方法：本回顾性队列研究使用2012年至2023年间荷兰索菲亚儿童医院收治的NF1伴PNs患者的临床病历数据，评估了临床表型的决定因素及预测结局的PN特征，包括PN复杂性和干预时机。通过逻辑回归分析和Cox回归评估结局。 结果：共纳入90例患者，末次评估中位年龄15.7岁，中位随访时间9.8年。在90例良性PN患者中，37例在随访期间出现丛状神经纤维瘤相关发病率。校正致病性NF1变异和PN位置后，年龄增长与丛状神经纤维瘤发病率显著相关。Cox回归显示，与肢体PNs相比，颅面部和躯干PNs具有更高的干预风险。 结论：我们的初步多变量分析发现，年龄增长和PN位置与丛状神经纤维瘤发病率升高及干预风险增加密切相关。这可能有助于指导NF1伴PNs患者的治疗决策，包括确定治疗对象和启动时机。
肿瘤(癌症)患者之家