Long-Term Survivors of Childhood Cancer Exhibit Vascular Endothelial Damage
In a study reported in Journal of Clinical Oncology, Cornelia A.J. Brouwer, of the University Medical Center Groningen in the Netherlands, and colleagues assessed vascular parameters in long-term childhood cancer survivors and sibling controls. They found that survivors who had received radiotherapy as part of their treatment had an unfavorable cardiovascular risk profile including increased carotid and femoral intima-media thickness and higher tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-I) levels.
Study Details
In the study, vascular assessment was performed in 277 adult survivors of childhood cancer with a median age at diagnosis of 9 years (range 0-20 years) and current median age of 28 years (range 18-48 years) who had been treated with potentially cardiovascular toxic anticancer treatments including anthracyclines, platinums, and radiotherapy. Measurements included carotid- and femoral-wall intima-media thickness, flow-mediated vasodilatation of the brachial artery by ultrasound, assessment of endothelial and inflammatory marker proteins including t-PA and PAI-I, and cardiovascular risk factors. Assessments were compared with those in 130 sibling controls with a median age of 26 years (range 18-51).
Evidence of Endothelial Damage
At a median of 18 years (range 5-31 years) after treatment, carotid and femoral IMTs did not differ in survivors vs controls; survivors exhibited significantly reduced carotid distensibility and mean pressure pulsations and significantly increased median t-PA and PAI-I levels and albumin to creatinine ratio. Survivors who received radiotherapy as part of their treatment (n = 174) had increased carotid (P = .036) and femoral (P = .032) intima-media thickness and higher t-PA and PAI-I levels, indicating vascular damage and persistent endothelial activation.
Patients treated with total body irradiation had higher t-PA (median 7.4 vs 4.5 ng/mL, P = .001) and PAI-I (median 26 vs 13 ng/mL, P < .001) levels than patients receiving no radiotherapy. Patients treated with radiotherapy to the neck, chest, or mediastinum (n = 26) also had greater femoral intima-media thickness (P = .018) than patients receiving no radiotherapy. Greater carotid intima-media thickness was significantly associated with presence of hypertension (P = .018) and overweight (P<.001).
The investigators concluded: “After potentially cardiovascular toxic anticancer treatment, [survivors] who received [radiotherapy] showed signs of endothelial damage and an unfavorable cardiovascular risk profile compared with controls. [Survivors] treated with localized [radiotherapy] had increased [intima-media thickness] outside the primary irradiation field. These abnormalities are probably involved in the pathogenesis of cardiovascular morbidity in childhood cancer survivors.”
Jourik A. Gietema, MD, PhD, of University Medical Center Groningen in the Netherlands, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the Quality of Life Gala 2003 Foundation.
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