Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

Robert Terziev,Jean-Yves Delattre,Caroline Dehais,Ahmed Idbaih,Damien Ricard,Dimitri Psimaras,Yannick Marie,Marc Sanson,Wolf Mueller,Julian Jacob,Loic Feuvret,Ben Kinnersley,Giulia Berzero,Khe Hoang-Xuan,Flavie Bompaire

doi:10.1038/s41598-021-89216-1

Abstract

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.

Highlights

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated
The treatment of high-grade (i.e., World Health Organization—WHO—grade III and grade IV) gliomas (HGG) includes surgery, radiotherapy (RT), and chemotherapy, which are associated with a median overall survival of 72 months in grade III and 14 months in grade IV gliomas[1]
We investigated the cumulative incidence of RIL in a cohort of long surviving HGG patients, with the aim of identifying individual risk factors for the development of this condition

Summary

Introduction

The incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. 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 latedelayed radiation-induced neurotoxicity. Radiation-induced leukoencephalopathy (RIL)[2] is the most common correlate of radiation toxicity and can be associated with a variety of neurological symptoms, including cognitive deficits, gait disturbances, and urinary incontinence, all reflecting an impairment of subcortical networks[3,4,5]. There are few published data on the incidence of radiation-induced leukoencephalopathy (RIL) in long surviving HGG patients and, some individual susceptibility factors have been suggested (e.g., age, vascular risk factors, genetic predisposition)[2,6], none has been convincingly demonstrated

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Conclusion