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

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.

Precision based approach to tailoring radiotherapy in the multidisciplinary management of pediatric central nervous system tumors

“… 136 Germline SNP on the peroxisome proliferator activated receptor gamma gene was associated with increased incidence of radiation induced leukoencephalopathy in a retrospective analysis. 137 GWAS can help tailor predictors of radiosensitivity or radiation induced toxicity to guide treatment and patient counseling.…”

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

“…The incidence and risk factors associated with IR-induced leukoencephalopathy in long-term survivors of HGG have been investigated by Terziev et al [90]. A retrospective research for patients with supratentorial HGG treated with focal RT that had a progression-free survival >30 months and available germline DNA was conducted.…”

“…Age > 60 years, smoking, and the germline SNP rs2120825 at the Peroxisome Proliferator-Activated Nuclear Receptor gamma (PPARg) locus were associated with an increased risk of leukoencephalopathy. PPARg agonists for the prevention and management of late-delayed RT-induced neurotoxicity have been proposed [90].…”

“…Age > 60 years, smoking, and rs2120825 germline SNP at the PPARg nuclear receptor locus were associated with an increased risk of leukoencephalopathy. PPARg agonists have been proposed for the prevention and management of this late RT-induced complication [90].…”

Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients

“…Following multimodal treatment in glioma patients, fiber connections may become disrupted by structural tissue damage resulting from tumor resection, radiotherapy, alkylating chemotherapy, or combinations thereof ( 10 – 13 ), or by recurrent tumor growth ( 14 ). Apart from the fiber tracts originating in the primary, eloquent cortical regions, tissue damage may affect larger and wider distributed white matter areas ( 15 – 17 ) involving structural connections of multiple functional networks ( 18 ). Therefore, glioma patients often develop deficits in cognition, general performance ( 19 ), and quality of life that increase with the duration of survival and intensity of therapy ( 15 , 20 ).…”