Service de Neurologie 2-Mazarin, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, 75013, Paris, France.
Department of Neuro-Pathology, University of Leipzig, 04103, Leipzig, Germany.
Sci Rep. 2021 May 13;11(1):10176. doi: 10.1038/s41598-021-89216-1.
The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18-69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.
放射性脑白质病（RIL）在高级别胶质瘤（HGG）长期幸存者中的发病率和相关风险因素仍研究甚少。我们对在我院接受局部放疗的幕上 HGG 患者的机构数据库进行了回顾性研究，这些患者的无进展总生存期（PFS）>30 个月，并且有可利用的种系 DNA。我们对 T2/FLAIR 序列上的脑白质病的 MRI 扫描进行了复查，并对脑血管危险因素和神经症状的医疗记录进行了审查。我们研究了一组候选单核苷酸多态性（SNP），以评估遗传风险。共纳入 81 例 HGG 患者（18 例 IV 级和 63 例 III 级，50 例男性/31 例女性）。放疗时的中位年龄为 48 岁（18-69 岁）。放疗完成后的中位随访时间为 79 个月。在随访期间，共有 44 例（44/81，54.3%）患者发生 RIL。在这 44 例患者中，29 例（29/44）出现了皮质下痴呆（n=28）、步态障碍（n=12）和尿失禁（n=9）等一致的症状。RIL 的累积发生率为 12 个月时为 21%，36 个月时为 42%，60 个月时为 48%。年龄>60 岁、吸烟和种系 SNP rs2120825（PPARg 基因座）与 RIL 风险增加相关。我们的研究确定了 RIL 发展的潜在风险因素（年龄、吸烟和种系 SNP rs2120825），并为测试 PPARg 激动剂在预防和管理迟发性放射性神经毒性方面提供了依据。
