Endothelial damage in long-term survivors of childhood cancer.
OBJECTIVE
To evaluate the presence of vascular damage in long-term childhood cancer survivors (CCS) and sibling controls, and to evaluate the association between vascular damage parameters and cancer treatment and influence of cardiovascular risk factors.


METHODS
Vascular assessment was performed in 277 adult CCSs (median age at diagnosis, 9 years; range, 0 to 20 years; median current age, 28 years; range, 18 to 48 years) treated with potentially cardiovascular toxic anticancer treatment (ie, anthracyclines, platinum, and/or radiotherapy [RT]). Measurements included carotid- and femoral-wall intima-media thickness (IMT), flow-mediated vasodilatation of the brachial artery by ultrasound, assessment of endothelial and inflammatory marker proteins (including tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor type 1 [PAI-I]), and cardiovascular risk factors. CCS assessments were compared with those of 130 sibling controls (median age, 26 years; range, 18 to 51 years).


RESULTS
At a median of 18 years (range, 5 to 31 years) after treatment, carotid and femoral IMTs in CCSs were not different from those of controls. However, CCSs who received RT as part of their treatment regimen had increased carotid and femoral IMTs and higher t-PA and PAI-I levels, indicating vascular damage and persistent endothelial activation. Patients treated with RT to the neck or chest also had greater femoral IMT. Greater IMT was associated with presence of cardiovascular risk factors (eg, hypertension and overweight).


CONCLUSIONS
After potentially cardiovascular toxic anticancer treatment, CCSs who received RT showed signs of endothelial damage and an unfavorable cardiovascular risk profile compared with controls. CCSs treated with localized RT had increased IMT outside the primary irradiation field. These abnormalities are probably involved in the pathogenesis of cardiovascular morbidity in CCSs.
Cornelia A.J. Brouwer, Aleida Postma, H. Louise H. Hooimeijer, Andries J. Smit, Judith M. Vonk, Arie M. van Roon, Maarten P. van den Berg, Wil V. Dolsma, Joop D. Lefrandt, Margreet T.E. Bink-Boelkens, Nynke Zwart, Wim J.E. Tissing, Elisabeth G.E. de Vries, and Jourik A. Gietema, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Cornelia A J
CA
Brouwer
Aleida
A
Postma
H Louise H
HL
Hooimeijer
Andries J
AJ
Smit
Judith M
JM
Vonk
Arie M
AM
van Roon
Maarten P
MP
van den Berg
Wil V
WV
Dolsma
Joop D
JD
Lefrandt
Margreet T E
MT
Bink-Boelkens
Nynke
N
Zwart
Elisabeth G E
EG
de Vries
Wim J E
WJ
Tissing
Jourik A
JA
Gietema
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D059168:Carotid Intima-Media Thickness; D002648:Child; D002675:Child, Preschool; D004727:Endothelium / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D011878:Radiotherapy / Q000009:adverse effects; D017741:Survivors / Q000706:statistics & numerical data*; D055815:Young Adult
D000970:Antineoplastic Agents