Late-Occurring Stroke Among Long-Term Survivors of Childhood Leukemia and Brain Tumors: A Report From the Childhood Cancer Survivor Study

Memorial Sloan-Kettering Cancer Center, New York, New York, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 12/2006; 24(33):5277-82. DOI: 10.1200/JCO.2006.07.2884
Source: PubMed


This report examines the incidence of and risk factors for strokes that occur in > or = 5-year survivors of childhood leukemia and brain tumors.
The rate of first occurrence of self-reported late-occurring strokes was determined for leukemia survivors (n = 4,828), brain tumor survivors (n = 1,871), and a comparison group of a random sample of cancer survivor siblings (n = 3,846). Relative risks (RRs) and 95% confidence intervals (CIs) of stroke by treatment exposures were examined by multivariate analyses.
Thirty-seven leukemia survivors and 63 brain tumor survivors reported a late-occurring stroke. The rate of late-occurring stroke for leukemia survivors was 57.9 per 100,000 person-years (95% CI, 41.2 to 78.7). The RR of stroke for leukemia survivors compared with the sibling comparison group was 6.4 (95% CI, 3.0 to 13.8; P < .0001). The rate of late-occurring stroke for brain tumor survivors was 267.6 per 100,000 person-years (95% CI, 206.8 to 339.2). The RR of stroke for brain tumor survivors compared with the sibling comparison group was 29.0 (95% CI, 13.8 to 60.6; P < .0001). Mean cranial radiation therapy (CRT) dose of > or = 30 Gy was associated with an increased risk in both leukemia and brain tumor survivors in a dose-dependent fashion, with the highest risk after doses of > or = 50 Gy CRT.
Survivors of childhood leukemia and brain tumors, particularly those with brain tumors treated with CRT at doses of greater than 30 Gy, are at an increased risk of stroke.


Available from: James G Gurney, Nov 09, 2015
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    • "Although considerable progress has been made in the treatment of childhood cancers, survivors experience significant late-effects such as atherosclerotic cardiovascular disease at a relatively higher rate compared to non-cancer sibling controls123. The pathogenesis of atherosclerotic cardiovascular disease is rooted in the vascular endothelial damage brought about by radiation and chemotherapy drugs like anthracyclines and cisplatin. "
    [Show abstract] [Hide abstract] ABSTRACT: Radiation during childhood cancer treatment increases the propensity to atherosclerotic cardiovascular disease among adult survivors of childhood cancer. This is thought to be mediated through the damage to the underlying vascular endothelium. Endothelial progenitor cells (EPCs) involved in vascular endothelial repair after its damage may be affected by radiation therapy but have never been investigated in adult survivors of childhood cancer. In this pilot study, utilizing multi-parametric flowcytometry, endothelial colony forming cells (ECFCs), which are the bonafide EPCs, and circulating endothelial cells (CECs), which are not EPCs, were compared between adult survivors of childhood cancer with or without radiation exposure. In addition, their associations with blood-pressure, physical activity and diet were examined. Survivors who received radiotherapy had lower ECFCs and CECs (p<0.05) compared to those without it. Significant positive correlations included physical activity with ECFCs and diet with CECs, while blood-pressure negatively correlated with ECFCs. Further evaluation is needed to examine the effect of radiation and modifiable risk factors on ECFCs and CECs. The preliminary findings from this study suggest evidence of the role of ECFCs as biomarkers of vascular injury following treatment for childhood cancer that may help in early identification of survivors at risk for cardiovascular disease.
    Full-text · Article · Aug 2015
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    • "As in HL, radiation therapy is believed to play an important role in the development of long-term toxicities. Some of the long-term toxicities recognized to date include moderate to severe neurological or cognitive impairment in 3–15% of patients, a sixfold increase in risk of stroke, a threefold increase in risk of short stature, infertility (in post-pubescent males) and secondary malignancies including brain tumors and secondary leukemia (Ise et al., 1986; Neglia et al., 1991; Relling et al., 1999; von der Weid and Swiss Pediatric Oncology Group, 2001; Bowers et al., 2006; Chow et al., 2007 ). In addition cytotoxic chemotherapy treatment is a recognized cause of “secondary” leukemias, with the risk reaching 5% for most ALL survivors and a 20% risk in survivors of T cell ALL at 6 years (Pui et al., 1989). "
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    • "It is well documented that radiotherapy can induce a type of vascular disease, termed vasculopathy.2)3) In addition, it has become increasingly evident that cranial radiation therapy increases the risk of stroke for cancer survivors.4)5) Although radiation-induced occlusive vasculopathies are well documented, little is known about the characteristics of radiation-induced intracranial aneurysms and their optimal treatment strategy. "
    [Show abstract] [Hide abstract] ABSTRACT: We report herein a case of a radiation-induced aneurysm. A 69-year-old woman presented with subarachnoid hemorrhage. Eight years previously, she had undergone cranial radiation therapy (total dose of 59.4 Gy) as adjuvant therapy after surgical resection for a chondrosarcoma that was destroying her sphenoid sinus. The patient underwent catheter angiography, which revealed an aneurysm of the anterior communicating artery and luminal narrowing and irregularity in the petrous and lacerum segments of the right internal carotid artery. We attempted surgical clipping of the aneurysm, but there was repeated bleeding. Finally the aneurysm was treated with endovascular trapping. Potentially fatal bleeding also occurred from her internal carotid artery, which had also been irradiated during the previous cranial radiation therapy. We stopped the bleeding with endovascular coil embolization. Because of diffuse vascular changes of the cerebral vessels within irradiated fields, special attention must be paid to their treatment.
    Full-text · Article · Dec 2012
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