Risk of Symptomatic Stroke After Radiation Therapy for Childhood Cancer: A Long-Term Follow-Up Cohort Analysis.
Long-term childhood cancer survivors are at high risk of late adverse effects, including stroke. We aimed to determine the cumulative incidence of clinically validated symptomatic stroke (transient ischemic attack [TIA], cerebral infarction, and intracerebral hemorrhage [ICH]) and to quantify dose-effect relationships for cranial radiation therapy (CRT) and supradiaphragmatic radiation therapy (SDRT).



Our single-center study cohort included 1362 survivors of childhood cancer that were diagnosed between 1966 and 1996. Prescribed CRT and SDRT doses were converted into the equivalent dose in 2-Gy fractions (EQD2). Multivariate Cox regression models were used to analyze the relationship between the EQD2 and stroke.



After a median latency time of 24.9 years and at a median age of 31.2 years, 28 survivors had experienced a first stroke: TIA (n=5), infarction (n=13), and ICH (n=10). At an attained age of 45 years, the estimated cumulative incidences, with death as competing risk, among survivors treated with CRT only, SDRT only, both CRT and SDRT, and neither CRT nor SDRT were, respectively, 10.0% (95% confidence interval [CI], 2.5%-17.0%), 5.4% (95% CI, 0%-17.0%), 12.5% (95% CI, 5.5%-18.9%), and 0.1% (95% CI, 0%-0.4%). Radiation at both locations significantly increased the risk of stroke in a dose-dependent manner (hazard ratios: HRCRT 1.02 Gy(-1); 95% CI, 1.01-1.03, and HRSDRT 1.04 Gy(-1); 95% CI, 1.02-1.05).



Childhood cancer survivors treated with CRT, SDRT, or both have a high stroke risk. One in 8 survivors treated at both locations will have experienced a symptomatic stroke at an attained age of 45 years. Further research on the pathophysiologic processes involved in stroke in this specific group of patients is needed to enable the development of tailored secondary prevention strategies.
Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: i.w.vandijk@amc.uva.nl.
Irma W E M
IW
van Dijk
Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Helena J H
HJ
van der Pal
Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands.
Rob M
RM
van Os
Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands.
Yvo B W E M
YB
Roos
Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Elske
E
Sieswerda
Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Elvira C
EC
van Dalen
Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Cécile M
CM
Ronckers
Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands.
Foppe
F
Oldenburger
Department of Epidemiology, Netherlands Cancer Institute, Academic Medical Center, Amsterdam, The Netherlands.
Flora E
FE
van Leeuwen
Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Huib N
HN
Caron
Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands.
Caro C E
CC
Koning
Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
Leontien C M
LC
Kremer
D000293:Adolescent; D000328:Adult; D015984:Causality; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D016371:Cranial Irradiation / Q000401:mortality* / Q000706:statistics & numerical data; D005260:Female; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000532:radiotherapy*; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011832:Radiation Injuries / Q000175:diagnosis / Q000401:mortality*; D011879:Radiotherapy Dosage; D012042:Registries; D018570:Risk Assessment; D020521:Stroke / Q000175:diagnosis / Q000401:mortality*; D015996:Survival Rate; D017741:Survivors; D063189:Symptom Assessment / Q000706:statistics & numerical data; D016896:Treatment Outcome; D055815:Young Adult