Because growth hormone (GH) treatment, often necessitated by childhood cancer GH deficiency, has been linked to tumorigenesis, concerns remain about its use in childhood cancer survivors.
New review findings show it is safe to administer growth hormone (GH) treatment to childhood cancer survivors, despite concerns about a possible link between the development of malignancies – both tumor recurrence and secondary neoplasm (SN) – and the therapy, researchers have determined. Still, they add that the magnitude of individual risk per patient should continue to be explored, as should the risk of SN during/after GH therapy in individuals with a history of cancer predisposition syndromes.
The findings on childhood cancer survivors (CCS) were published in Frontiers in Endocrinology.
“The long-term effects of GH treatment have been extensively studied, given the mitogenic properties of GH and its downstream insulin-like growth factor,” the authors wrote. “This is of particular importance in CCS, as they are a priori at higher risk of tumor recurrence and secondary tumors.”
Their primary aim was to gain a clearer picture of which CCS are most at risk for GH deficiency (GHD) and to profile the safety of the therapy in this patient group.
Using data from the Childhood Cancer Survivor Study, the authors showed that 22.5% of CCS develop 2 or more serious conditions by age 50, with an additional 9.6% developing 1 SN and 2, 6% developing 2 SNs. Risk factors include radiation exposure, family cancer history, and primary diagnosis of sarcoma or Hodgkin lymphoma. Previous research results have been mixed about the exact risks of GH therapy, due to “lack of standardization of laboratory tests and diagnostic thresholds for GHD,” the authors write. Still, they add that data indicates that GH treatment is likely safe.
Additional study results on childhood brain tumor recurrence, from studies comparing outcomes between GH treated and untreated patients, show no significant difference in tumor recurrence, and central nervous system tumor data does not confirm an association between GH treatment with tumor recurrence. Also, in patients with a history of cancer, the risk of disease recurrence was not significantly different between individuals treated with GH and those who were not.
Several other studies in their analysis looked at possible links between patients with a history of skull radiation — particularly because radiation therapy is a known independent risk factor for GHD, especially at higher doses — and the potential to develop SNs. However, their findings here do not show a significant association between the risk of SN and the mean GH dose, duration of treatment and cumulative dose. In addition, patients with previous brain radiation treatment are at greater risk of meningiomas, and that may be a confounding factor when a possible link is seen between GH treatment and SN development.
Despite concerns that treatment for GHD – itself the outcome of previous cancer treatment – may give rise to tumor recurrence or SNs in CCS, the authors found no such association in their study analyses.
“There are theoretical concerns about the development of malignancies if GH therapy is initiated if GHD is diagnosed in the CCS,” the authors concluded. “However, the association between GH therapy and cancer has been extensively studied, and while many existing studies are limited by the lack of a comparator group, current data suggest that GH therapy does not increase tumor recurrence in CCS.”
Still, they recommended caution in generalizing their results due to a lack of long-term data on the association between GH therapy and cancer risk and the potential role of genetics in cancer development, especially in people with cancer predisposition syndrome. Because of this, they add, the risk-to-benefit ratio of GH treatment must be individualized.
Pollock NI, Cohen LE. Growth hormone deficiency and treatment in childhood cancer survivors. Anterior Endocrinol (Lausanne). Published online October 22, 2021. doi:10.3389/fendo.2021.745932
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