Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors

Author:

Remes Tiina Maria1ORCID,Suo-Palosaari Maria Helena2,Koskenkorva Päivi K T3,Sutela Anna K3,Toiviainen-Salo Sanna-Maria4,Arikoski Pekka M5,Arola Mikko O6,Heikkilä Vesa-Pekka7,Kapanen Mika8,Lähteenmäki Päivi Maria9,Lönnqvist Tuula R I10,Niiniviita Hannele11ORCID,Pokka Tytti M-L1,Porra Liisa12,Riikonen V Pekka5,Seppälä Jan13,Sirkiä Kirsti H14,Vanhanen Antti8,Rantala Heikki M J1,Harila-Saari Arja H15,Ojaniemi Marja K1

Affiliation:

1. Department of Pediatrics and Adolescence, PEDEGO Research Unit and Medical Research Center, Oulu University Hospital, and University of Oulu, Oulu, Finland

2. Department of Diagnostic Radiology, Oulu University Hospital, and University of Oulu, Research Unit of Medical Imaging, Physics, and Technology, Faculty of Medicine, University of Oulu, and Medical Research Center Oulu, University of Oulu, Oulu, Finland

3. Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland

4. Department of Pediatric Radiology, HUS Medical Imaging Center, Radiology, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland

5. Department of Pediatrics and Adolescence, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland

6. Department of Pediatrics, Tampere University Hospital, and University of Tampere, Tampere, Finland

7. Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland

8. Department of Oncology and Department of Medical Physics, Tampere University Hospital, Tampere, Finland

9. Department of Pediatrics and Adolescent Medicine, Turku University Hospital, and Turku University, Turku, Finland

10. Department of Child Neurology, Children’s Hospital, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland

11. Department of Medical Physics, Division of Medical Imaging, Turku University Hospital, Turku, Finland

12. Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

13. Center of Oncology, Kuopio University Hospital, Kuopio, Finland

14. Department of Pediatrics and Adolescence, Helsinki University, and Helsinki University Hospital, Helsinki, Finland

15. Uppsala University, Department of Women’s and Children’s Health, Akademiska sjukhuset, Uppsala, Sweden

Abstract

Abstract Background Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy. Methods Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients’ files. Results Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts. Conclusions Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.

Funder

Health Research in the Department of Pediatrics and Adolescence

Väre Foundation for Pediatric Cancer Research

Foundation of Päivikki and Sakari Sohlberg

Foundation of Arvo and Lea Ylppö

Foundation for Pediatric Research

Foundation of Emil Aaltonen

Foundation of Thelma Mäkikyrö

Cancer Foundation of Northern Finland

Foundation of Alma

Foundation of Märta Donner

Cancer Society of Finland

Publisher

Oxford University Press (OUP)

Subject

Medicine (miscellaneous)

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