Because treatment with growth hormone (GH), often necessitated by GH deficiency from childhood cancer, has been linked to tumorigenesis, concerns remain around its use among childhood cancer survivors.
New review findings show it is safe to administer growth hormone (GH) treatment to pediatric cancer survivors, despite concerns over a potential link between malignancy development—both tumor recurrence and secondary neoplasm (SN)—and the therapy, investigators have determined. Still, they add, the extent of individual risk per patient should continue to be investigated, as should the risk of SN during/after GH therapy among persons 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 target insulin-like growth factor,” the authors wrote. “This is of particular concern in CCS, as they are at higher risk a priori of tumor recurrence and secondary tumors.”
Their primary goal was to get a more clear picture of which CCS are at greatest risk for GH deficiency (GHD) and to profile the safety of the therapy among this patient group.
Using data from the Childhood Cancer Survivor Study, the authors showed that 22.5% of CCS go on to develop 2 or more serious conditions by age 50 years, 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 study results have been mixed on the exact risks presented by GH therapy, due to “lack of standardization of laboratory assays and diagnostic thresholds for GHD,” the authors write. Still, they add, data do indicate that GH treatment is likely safe.
Additional study results on brain tumor recurrence in children, from investigations comparing outcomes between patients who were and were not treated with GH, show no significant difference in recurrent tumors, and data on central nervous system tumors do not bear out a link between GH treatment with tumor recurrence. Also, among patients with a previous cancer history, disease recurrence risk did not significantly differ between persons treated with GH and those who were not.
Several other studies in their analysis looked into possible connections between patients with a history of cranial irradiation—in particular because radiation therapy is a known independent risk factor for GHD, especially at higher doses—and potential to develop SNs. However, their findings here show no significant association between risk of SN and mean GH dose, treatment duration, and cumulative dose. In addition, patients with previous brain radiation treatment have greater risk of meningiomas, and that can be a confounding factor when a potential link is seen between GH treatment and SN development.
Overall, despite concerns that treatment for GHD—itself the result of previous cancer treatment—may give rise to tumor recurrence or SNs in CCS, the authors did not find such a connection in their study analyses.
“There are theoretical concerns about malignancy development 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 investigated, and while many existing studies are limited by lack of a comparison group, the current data suggest that GH therapy does not increase tumor recurrence in CCS.”
Still, they recommended exercising caution on generalizing their results due to lack of long-term data on the connection between GH therapy and cancer risk and the potential role of genetics in cancer development, especially among those with cancer predisposition syndrome. Because of this, they add, the risk-vs-benefit ratio of GH treatment should be individualized.
Pollock NI, Cohen LE. Growth hormone deficiency and treatment in childhood cancer survivors. Front Endocrinol (Lausanne). Published online October 22, 2021. doi:10.3389/fendo.2021.745932