ESPE Yearbook of Paediatric Endocrinology

Eur J Endocrinol. 2020; 183: 471–480. https://pubmed.ncbi.nlm.nih.gov/32738133/

This cohort and nested case–control study analyzed the impact of growth hormone (GH) treatment on the risk of second neoplasm (SN) in a French cohort of 2852 childhood cancer survivors (CCS) treated before 1986. In total, 126 (64.3%) survivors who received GH had been treated for a brain tumor, 22 (11.2%) for a retinoblastoma, 20 (10.2%) for a lymphoma and 28 (14.3%) for another type of solid tumor; 374 survivors developed a SN, including 40 who had received GH therapy. In multivariate analysis, GH treatment did not increase the risk of secondary non-meningioma brain tumors, secondary non-brain cancer, or meningioma. Slight non-significant increases in the risk of meningioma (1.6-fold) were observed after an exposure to GH of less than 4 years vs 2.3-fold after a longer exposure.

CCS receiving radiation therapy have a high risk of developing a subsequent radiation-induced SN. Radiation dose confounds the relationship between GH and the occurrence of a second CNS neoplasm, as higher doses are associated with both a higher likelihood of both GH deficiency and SN. Previous studies on CCS suggested that meningioma is diagnosed earlier in GH-treated survivors (1), but it is unclear if this is simply due to more careful follow up in GH-treated patients. The risk of meningioma is linearly related to radiation dose (568-fold higher risk at >30 Gy) (2).

In this study, the small number of meningioma cases compared to the numerous cofactors influencing the risk of meningioma (such as higher cranial radiation dose, younger age at cancer diagnosis and associated cancer predisposition syndromes), could have limited statistical power. The impact of GH dose, IGF-1 levels during GH treatment and the use of cadaveric vs recombinant GH were not analyzed. Finally, these data may not be confirmed in patients treated with new techniques of radiation therapy. A recent meta-analysis showed that GH therapy does not increase the risk of SN and improves final height, lipid profiles and quality of life in survivors of childhood cancer (3).

Reference: 1. Patterson BC, Chen Y, Sklar CA, Neglia J, Yasui Y, Mertens A, Armstrong GT, Meadows A, Stovall M, Robison LL et al. Growth hormone exposure as a risk factor for the development of subsequent neoplasms of the central nervous system: a report from the Childhood Cancer Survivor Study. Journal of Clinical Endocrinology and Metabolism. 2014; 99: 2030–7.2. Taylor AJ, Little MP, Winter DL, Sugden E, Ellison DW, Stiller CA, Stovall M, Frobisher C, Lancashire ER, Reulen RC et al. Population based risks of CNS tumors in survivors of childhood cancer: the British childhood cancer survivor study. Journal of Clinical Oncology. 2010; 28: 5287–93.3. Tamhane S, Sfeir JG, Kittah NEN, Jasim S, Chemaitilly W, Cohen LE & Murad MH. GH therapy in childhood cancer survivors: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2018; 103: 2794–801.