Background:
Among childhood cancer survivors, cranial radiation therapy (CRT) increases risk of self-reported first-stroke; there are no published estimates of recurrent stroke.
Objective:
To assess rates and predictors of first and recurrent stroke in childhood cancer survivors treated with CRT.
Methods:
In a retrospective cohort study of all children who received CRT at one institution,1980-2009, we performed chart abstraction (n=321) and phone interviews (n=101) to measure first and recurrent stroke; we confirmed stroke through imaging review. Incidence of first-stroke was calculated as the number of first strokes per person-years of observation after radiation. We used survival analysis techniques to determine the cumulative incidence of first stroke after radiation, and recurrent stroke after first stroke; we used Cox proportional hazards models to examine potential predictors of first stroke.
Results:
Median age of children at the time of CRT treatment was 8 years (IQR 4-13 years). A total of 17 first-strokes (12 ischemic, 2 hemorrhagic, 3 unknown sub-type) were identified at a median age of 25 years (IQR 17-34 years): 6 from chart review, 8 from interview, 3 from both. Imaging was available in 12 cases and consistent with stroke in all. The overall rate of first-stroke was 594 (95% CI 346 - 949) per 100,000 person-years. The risk of stroke persists for decades after treatment (see
Figure
). Males had a 4-fold hazard of first stroke compared to females (95% CI 1.1 - 14;
P
=0.034). Race and treatment with chemotherapy did not affect the stroke risk; dose effect of CRT could not be assessed due to a narrow dose range in our cohort. There were 5 recurrent strokes (2 ischemic, 2 hemorrhagic, 1 unknown) at a median of 6 months after first stroke (range 5.6 months to 8.9 years); brain imaging was available in 4 cases and consistent with stroke in all. The cumulative incidence of recurrent stroke was 21% (95% CI 7.5-53) at 1 year post first-stroke, 29% (95% CI 12-61) at 5 years, and 43% (95% CI 19-78) at 10 years.
Conclusion:
Survivors of childhood cancer who received CRT are at high risk for first and recurrent stroke. Larger studies are needed to identify predictors of recurrence to design secondary stroke prevention strategies.
Dental Abnormalities in Childhood Cancer Survivors Treated with Radiation Therapy to the Head-and-Neck: A Report from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Group
