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In childhood cancer survivors, GH therapy improves height without secondary tumor risk

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July 10, 2018

In childhood cancer survivors, treatment with growth hormone was associated with gains in height vs. untreated control patients without increased risk for diabetes or secondary tumors, according to a meta-analysis published in The Journal of Clinical Endocrinology & Metabolism.

“GH [deficiency] is one of the most common endocrinopathies observed in [childhood cancer survivors] with a history of central nervous system tumors,” M. Hassan Murad, MD, a clinical epidemiologist and director of the Evidence-Based Practice Research Program at Mayo Clinic in Rochester, Minnesota, and colleagues wrote in the study background. “Studies have shown that cancer and its treatments negatively impact adult height and that [childhood cancer survivors] may not fully recover their growth potential even after GH therapy.”

In a meta-analysis and review, Murad and colleagues conducted a database analysis to identify 16 observational studies that included 512 childhood cancer survivors who received an average GH dose of 0.3 IU/kg to 0.9 IU/kg per week, as well as control groups of childhood cancer survivors who received no GH treatment. For each study, researchers recorded baseline age, tumor type, radiation details, serum GH levels, GH dose and duration of GH therapy for patients. Outcomes of interest were focused on adult height, risk for diabetes, abnormal lipids, metabolic syndrome, quality of life, secondary tumors, disease recurrence and mortality. Researchers used random-effects meta-analysis to combine outcomes.

The researchers found that significant height gains were attained by childhood cancer survivors who underwent GH treatment vs. those not treated with GH (weighted mean difference, 0.61; 95% CI, 0.08-1.13; n = six studies). GH was not associated with any statistically significant differences in the incidence of secondary tumors (OR = 1.1; 95% CI, 0.72-1.67; n = five studies) or increased risk of disease or tumor recurrence (OR = 0.57; 95% CI, 0.31-1.02; n = eight studies). The researchers found that there was substantial heterogeneity for height analysis (I2 > 90%) and, to a lesser degree, tumor recurrence analysis (I2 > 60%). Homogeneity was found in the analysis of secondary tumors (I2 = 0%).

The results of the studies suggested either improvement or no change in diabetes risk, lipid profile abnormalities, metabolic syndrome and quality of life among patients treated with GH vs. untreated patients.

Researchers noted a positive association between adult height and the following: age at tumor therapy conclusion, height at the start of GH therapy, gain in height standard deviation score after the first year of GH therapy, age at diagnosis, age at irradiation, target height, dose of GH therapy, lower dose of radiation, and concomitant treatment with a gonadotropin-releasing hormone agonist. A negative association was seen between craniospinal irradiation, spinal radiation, dose of chemotherapy and the existence of other endocrinopathies.

Overall, there were moderate risks of bias in the included studies, owing primarily to inability to control the analysis for confounders, according to the researchers. Due to the observational nature of the evidence, the moderate risk of bias and imprecision, the quality of evidence was considered low.

“GH [therapy] is effective in increasing height in [childhood cancer survivors] with GH [deficiency],” the researchers wrote. “From the limited data available, no increased cardiovascular or metabolic risks were obviously associated with GH [therapy], but short follow-up time must be considered a limitation. Although this meta-analysis did not show increased risks of recurrence or secondary neoplasms, additional studies on these risks are necessary.”

The meta-analysis was one of two reviews conducted to support the Endocrine Society’s new clinical practice guideline, which stresses that childhood cancer survivors who underwent radiation therapy should be screened regularly for growth disorders, pituitary hormone deficiencies and early puberty. The second review aimed to determine the best screening and diagnostic tests for GH deficiency in childhood cancer survivors exposed to hypothalamic-pituitary radiation, while noting a high variability in the confirmatory testing each study used. – by Jennifer Byrne

Disclosures: The Endocrine Society funded this study. One of the study authors reports he serves as a consultant for Pfizer, and another author reports she has received honoraria from Scherer Clinical Communications through a grant from Novo Nordisk.