Impact of treatment exposures on cardiovascular risk and insulin resistance in childhoood cancer survivors
Menée auprès de 319 cas et de 208 témoins, cette étude évalue l'impact des traitements du cancer sur la résistance à l'insuline et le risque de maladies cardiovasculaires chez des survivants d'un cancer de l'enfance
Background: Childhood cancer survivors (CCS) are more insulin resistant (IR) and have higher levels of several cardiovascular (CV) risk factors even while still children. This study examines specific treatment exposures associated with CV risk factors and IR. Methods: CCS age 9-18 years at study entry and in remission >5 years from diagnosis (n=319) and 208 sibling controls were recruited into this cross-sectional study that included physiologic assessment of IR (hyperinsulinemic euglycemic clamp) and assessment of CV risk factors.. Regression and recursive tree modeling were used to ascertain treatment combinations associated with IR and CV risk. Results: Mean current age of CCS was 14.5yr, 54% were male (siblings 13.6yr, 54% male). Diagnoses included leukemia (35%), brain tumors (36%), solid tumors (33%) or lymphoma (6%). Among CCS, analysis of individual chemotherapy agents failed to find associations with CV risk factors or IR. Compared to siblings, IR was significantly higher in CCS who received platinum plus cranial radiation (CRT, 92% brain tumors) and in those who received steroids but no platinum (majority leukemia). IR did not differ between CCS who received surgery alone vs. siblings. Within survivor comparisons failed to elucidate treatment combinations that increased IR compared to those who received surgery only. Conclusions: Exposure to platinum, CRT or steroids is associated with IR and CV risk factors and should be taken into consideration in the development of screening recommendations for CV risk. Impact: Earlier identification of CCS who may benefit from targeted prevention efforts may reduce their future risk of CV disease.