Metabolic/endocrine disorders in survivors of childhood-onset and cranial radiotherapy- treated ALL/NHL: a meta-analysis

BACKGROUND: Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin’s lymphoma (ALL/NHL). However, effects of CRT treatment on the development of metabolic/endocrine disorders remain unclear. This meta-analysis aimed to identify metabolic and endocrine disturbances in survivors of childhood-onset and CRT-treated ALL/NHL. METHODS: Different online databases were searched using restricted search fields. Follow-up data and outcome measurements, including the prevalence of growth hormone (GH) deficiency, hypothyroidism, vitamin D deficiency, overweight/obesity, and hypogonadism were recorded. The height data was indicated by height-standard deviation score (height-SDS). Statistical estimates such as odds ratio (OR) and weighted standard mean difference (SMD) were compared between additional CRT treatment group and non-CRT treatment group. Study-to-study heterogeneity was calculated by calculating I-squared statistic, and fixed/random effect was applied to synthesize and analyze extracted data. RESULTS: Fifteen studies were included (4269 patients in total). Adult height SDS was lower in CRT-treated patients (pooled SMD = -0.581, 95% CI: -0.649–-0.512), and CRT-treated patients were likely to develop short stature (pooled OR = 2.289, 95% CI:1.674–3.130). Regardless of the study year, which potentially reflects the state-of-the-art CRT technique, the prevalence of short stature and GH deficiency was time-independent. Additionally, previous CRT can increase the risk of precocious puberty (pooled OR = 2.937, 95% CI: 1.281–6.736), hypothyroidism (pooled OR = 2.057, 95% CI:1.510–2.801), and hypogonadism (pooled OR = 3.098, 95% CI:2.521–3.807). However, the risk of being overweight/obese was similar between the patients with and without CRT (pooled OR = 1.278, 95% CI: 0.675–2.421). CONCLUSION: Childhood-onset and CRT-treated ALL/NHL survivors are likely to have shorter height, precocious puberty, hypothyroidism, and hypogonadism.