Table 10. Metabolic Syndrome Late Effects
|Predisposing Therapy||Potential Late Effects||Health Screening|
|BMI = body mass index.|
|Total-body irradiation||Metabolic syndrome||Exam (annual): height, weight, BMI, blood pressure|
|Labs: fasting glucose and lipids every 2 years|
Changes in Body Composition: Obesity and Body Fatness
To date, the primary cancer groups recognized with an increased incidence of treatment-related obesity are ALL [69,70,71,72,73,74,75,76,77,78,79,80,81,82,83] and CNS tumor [21,22,84] survivors treated with cranial radiation therapy.[85,86] In addition, craniopharyngioma survivors also have a substantially increased risk of extreme obesity due to the tumor location and the hypothalamic-pituitary-adrenal (HPA) damage resulting from surgical resection.[87,88,89,90,91,92,93]
In addition to treatment factors, lifestyle factors and medication use can also contribute to the risk of obesity. CCSS investigators reported the following independent risk factors for obesity in childhood cancer survivors:
- Cancer diagnosed at ages 5 to 9 years (RR, 1.12; 95% CI, 1.01-1.24).
- Abnormal physical functioning (RR, 1.19; 95% CI, 1.06-1.33).
- Hypothalamic/pituitary radiation dose of 20 Gy to 30 Gy (RR, 1.17; 95% CI, 1.05-1.3; P = .01).
- Specific antidepressant use (paroxetine) (RR, 1.29; 95% CI, 1.08-1.54).
Survivors who adhered to the U.S. Centers for Disease Control and Prevention guidelines for vigorous physical activity (RR, 0.90; 95% CI, 0.82-0.97; P = .01) and who had a medium amount of anxiety (RR, 0.86; 95% CI, 0.75-0.99; P = .04) had a lower risk of obesity.
Moderate-dose cranial radiation therapy (18-24 Gy) among ALL survivors is associated with obesity, particularly in females treated at a young age.[60,73,79,95] Female adult survivors of childhood ALL who were treated with cranial radiation therapy of 24 Gy prior to age 5 years are four times more likely to be obese in comparison with women who have not been treated for a cancer. In addition, women treated with 18 Gy to 24 Gy cranial radiation therapy prior to age 10 years have a substantially greater rate of increase in their BMI through their young adult years in comparison with women who were treated for ALL with only chemotherapy or with women in the general population. It appears that these women also have a significantly increased visceral adiposity and associated insulin resistance.[96,97] These outcomes are attenuated in males. Interestingly, among brain tumor survivors treated with higher doses of cranial radiation therapy, only females treated at a younger age appear to be at increased risk for obesity. The development of obesity following cranial radiation therapy is multifactorial, with factors including GHD, leptin sensitivity, reduced levels of physical activity, and energy expenditure.[79,99,100] Importantly, survivors of childhood cancer treated with TBI in preparation for an allogeneic HSCT have increased measures of body fatness (percent fat) while often having a normal BMI.[67,101]
It remains controversial whether contemporary ALL therapy, without cranial radiation therapy, is associated with a sustained increase in BMI. During and soon after completion of therapy, there appears to be an increase in BMI z-scores among children treated for ALL with only chemotherapy.[80,81,82,102] However, investigators from the CCSS did not find a significant association among adult survivors of childhood ALL between chemotherapy-only protocols and risk of obesity or change in BMI over time. Notably, while there may not be an increased incidence of obesity, as measured by BMI, among adult survivors of childhood ALL, there does appear to be an increase in percent body fat [78,83,97,103] and visceral adiposity.