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Pilot study of vascular health in survivors of osteosarcoma

Authors :
Aaron S. Kelly
Joseph P. Neglia
Daniel A. Mulrooney
Robert P. Hebbel
Kirsten K. Ness
James D. Neaton
Denis R. Clohisy
Anna Solovey
Sujuan Huang
Source :
Pediatric Blood & Cancer. 60:1703-1708
Publication Year :
2013
Publisher :
Wiley, 2013.

Abstract

300mg/m 2 or more of anthracyclines (N ¼14) or treated with multi-agent chemotherapy (with or without cranial radiation) for ALL (N ¼75) compared to healthy controls [11,12]. The complex mechanisms of cardiovascular injury remain poorly defined and additional study is needed to help guide the testing of therapeutic interventions. The objective of this study was to assess markers of vascular injury among survivors of osteosarcoma, a population with intensive, potentially vascular toxic, chemotherapy exposures, typically without radiation exposure. We previously collected the same biomarkers among survivors of Hodgkin lymphoma and found evidence suggestive of vascular inflammation, dyslipidemia, Background. Cardiovascular-related toxicities have been reported among survivors of osteosarcoma. Methods. Fasting blood samples from 24 osteosarcoma survivors were analyzed for highsensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein-s, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and surface expression of vascular cell adhesion molecule-1 (VCAM-1). Values were compared to subjects in the natural history Coronary Artery Risk Development in Young Adults (CARDIA) cohort study except for CECs and VCAM-1 expression, which were compared to controls studied at the University of Minnesota Lillehei clinical trials unit. Procedure. Survivors (54.2% male), median age 18 years (9–32) at diagnosis,36.5years(20–56)atevaluationweretreatedwithavariety of chemotherapeutic exposures, all but one were exposed to doxorubicin (median dose 450mg/m 2 ; range: 90–645mg/m 2 ), 14 (58.3%) received cisplatin, and 3 (12.5%) were exposed to carboplatin. Two survivors (8.3%) received radiation therapy for disease relapse. Compared to CARDIA subjects, mean hsCRP (3.0mg/L � 2.0 vs. 1.6 � 2.3), triglycerides (151mg/dl � 81.7 vs. 95.4 � 101.3),lipoprotein(a)(34.9mg/dl � 17.7vs.13.8 � 22.0),and fibrinogen (315.0mg/dl � 49.3 vs. 252.4 � 61.7) were significantly elevated. The number of CECs (0.47cells/ml � 2.5 vs. 0.92 � 2.5) did not differ while surface expression of VCAM-1 (86.4% � 34.0 vs. 42.1 � 33.8) was significantly elevated compared to controls. Conclusions. Among survivors of osteosarcoma, assessed a median of 14 years from diagnosis, there is evidence of vascular inflammation, dyslipidemia, and early atherogenesis. Pediatr Blood Cancer 2013;60:1703–1708. # 2013 Wiley Periodicals, Inc.

Details

ISSN :
15455009
Volume :
60
Database :
OpenAIRE
Journal :
Pediatric Blood & Cancer
Accession number :
edsair.doi...........445ff47d30eeb83e4df5e04922097b0a