Stroke and Stroke Recurrence May Increase Mortality in Pediatric Cancer Survivors

Stroke and stroke recurrence may be associated with increased mortality and negatively impact health related quality of life (HRQOL) measures in survivors of pediatric cancer, according to a study published in Cancer.

As therapies continue to improve for pediatric patients with cancer and increase survivorship, it will be paramount for both pediatric and adult practitioners to identify those tumor survivors at greatest risk of poor long-term outcomes and low HRQOL. 

“Because incident stroke correlates with poorer HRQOL measures, there may be an indication to intervene sooner and more aggressively to prevent stroke in these survivors,” the researchers wrote. 

In this retrospective cohort of 14,358 participants with pediatric cancer, 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2,636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. 

Among 7,304 survivors, those who had had a stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3; 95% CI, 1.4-3.8; and recurrent stroke OR, 5.3; 95% CI, 1.7-16.8) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4; 95% CI, 1.4-4.1; and recurrent stroke OR, 3.3; 95% CI, 1.1-10.3) and memory (single stroke OR, 2.1; 95% CI, 1.2-3.7; and recurrent stroke OR, 3.5; 95% CI, 1.1-10.5). 

Additionally, stroke history was found to be associated with an elevated risk of an inability to work rather than being employed, and this risk tripled between survivors with single and recurrent strokes (OR for single stroke, 3.2; 95% CI, 1.8-5.7; P < .001; and OR for recurrent stroke, 9.5; 95% CI, 3.2-27.9; P < .001). Notably, survivors who experienced a second stroke were much more likely to report “no recovery” from the stroke (first stroke rate of no recovery of 8.86% vs second stroke rate of no recovery of 26.3%). 

“Overall, all-cause mortality as well as health-related mortality increased by >3-fold in cancer survivors who experienced repeated strokes compared with those with no stroke history,” the researchers explained.

Stroke risk in patients who previously had pediatric cancer has been associated with dose-dependent exposure to chemoradiation (CRT) in the past. However, the majority of patients in the current study did not receive CRT or received only low-dose exposure (<20 grays). 

Researchers suggested that recommendations to screen and potentially intervene with regard to stroke risk in survivors of pediatric cancer might need to be implemented more aggressively. The current data supports close screening and potential aggressive interventions when possible.

The link between stroke and long-term outcomes is presumably a combined effect of stroke-related neurocognitive injury, ongoing medical management in the poststroke period, and the burden of a new life-threatening event in a patient who has previously experienced one life-threatening diagnosis, among other stressors. 

Large prospective studies are necessary to more completely isolate the etiology of why such a high percentage of survivors of pediatric cancer who experience stroke go on to develop negative HRQOL and psychosocial outcomes. 

Participants were diagnosed between January 1, 1970 and December 31, 1999 and aged <21 years at time of diagnosis. The cohort contained a longitudinal follow-up of 5-year survivors of common pediatric cancer, including leukemia, brain tumors, Hodgkin lymphoma, non-Hodgkin lymphoma, bone tumors, soft-tissue sarcomas, kidney tumors, and neuroblastoma. 

There are now almost 430,000 survivors of childhood cancer in the U.S. according to the study. 

Reference:

Mueller S, Kline CN, Buerki RA, et al. Stroke Impact on Mortality and Psychologic Morbidity Within the Childhood Cancer Survivor Study. Cancer. doi:10.1002/cncr.32612.