Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study

Sävendahl, Lars; Cooke, Rosie; Tidblad, Anders; Beckers, Dominique; Butler, Gary; Cianfarani, Stefano; Clayton, Peter E.; Coste, Joël; Hokken-Koelega, Anita C S; Kieß, Wieland; Kuehni, Claudia E.; Albertsson‐Wikland, Kerstin; Deodati, Annalisa; Écosse, Emmanuel; Gausche, Ruth; Giacomozzi, Claudio; Konrad, Daniel; Landier, F; Pfaeffle, Roland; Sommer, Grit; Thomas, Muriel; Tollerfield, Sally; Zandwijken, Gladys R J; Carel, Jean‐Claude; Swerdlow, Anthony J.

doi:10.1016/s2213-8587(20)30163-7

Cited by 70 publications

(67 citation statements)

References 27 publications

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“…Several other studies reporting on tumor recurrence or secondary tumors have been published, mostly in agreement with the result by Thomas-Teinturier et al, although there also have been some reports of increased risk for certain cancer types or with a trend toward increased risk of mortality (4,5,9,10). The studies reporting an increased risk of secondary cancer or mortality, must be interpreted precociously for three reasons; first, in most studies, due to the relatively small number of events, high confidence intervals and subsequent low levels of significance are present; secondly in many studies, the used control groups resulted in a high risk of outcome bias due to the fact that patients surviving childhood cancer receiving GH treatment already were at increased risk for mortality or a secondary neoplasms due to their history with more toxic therapies such as high dose chemotherapy, stem cell transplantation or radiotherapy.…”

Section: Comparing the Results With Other Published Studiessupporting

confidence: 84%

“…The studies reporting an increased risk of secondary cancer or mortality, must be interpreted precociously for three reasons; first, in most studies, due to the relatively small number of events, high confidence intervals and subsequent low levels of significance are present; secondly in many studies, the used control groups resulted in a high risk of outcome bias due to the fact that patients surviving childhood cancer receiving GH treatment already were at increased risk for mortality or a secondary neoplasms due to their history with more toxic therapies such as high dose chemotherapy, stem cell transplantation or radiotherapy. The increased cause-specific mortality of the children with cancer reported in the recent SAGhe study (4), was also interpreted to be associated with the underlying diagnosis. Favorably, future studies should be performed in a homogenous cancer survivor group, with the same tumor type and toxicity all with GHD, with and without GH treatment.…”

Section: Comparing the Results With Other Published Studiesmentioning

confidence: 99%

“…Unfortunately, such studies are not available. Thirdly, regarding the reported trend toward increased mortality, no significant relation of GH-dose or duration of GHRT on mortality was found, making a causal relation less likely (4,5). Nevertheless, GH therapy in high-risk patients should be given with care and the decision to start GH therapy should be carefully discussed with families (9).…”

Section: Comparing the Results With Other Published Studiesmentioning

confidence: 99%

Section: The Risk Of Developing Neoplasms During or After Gh Treatmenmentioning

confidence: 99%

“…In children with short stature, without underlying endocrine conditions such as children born small for gestational age (SGA), idiopathic short stature or Turner syndrome, GH treatment has not been associated with increased cancer risk (4). Also, for non-CCS GHD children, no increased risk to develop cancer was reported (4,5). The results of studies in these children cannot be compared to CCS, however, as CCS may have a different genetic profile or may have been treated with other toxic agents such as chemotherapy or radiotherapy, possibly influencing their (secondary) cancer risk.…”

Section: The Risk Of Developing Neoplasms During or After Gh Treatmenmentioning

confidence: 99%

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Safety of GH after treatment for childhood cancer

Santen

2020

European Journal of Endocrinology

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Dr Thomas Teinturier et al. describe the influence of growth hormone (GH) therapy on the development of second neoplasms in childhood cancer survivors (CCS)1. The manuscript is an important contribution to literature, as GH deficiency (GHD) is frequently observed in CCS, especially in the childhood brain tumor survivors after exposure to cranial irradiation or in children surviving a tumor in the hypothalamic-pituitary region. In their study, no increased risk was found for recurrence of the original tumor, nor for the development of a second tumor. A slight non significant increased risk is described for the development of meningioma, which may be confounded by previous radiotherapy. These results are reassuring for children who have been diagnosed with GHD after surviving a malignancy and who are treated with GH injections on a daily basis. There are however still some concerns and unanswered questions that need attention in future studies.

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Section: Comparing the Results With Other Published Studiessupporting

confidence: 84%

Section: Comparing the Results With Other Published Studiesmentioning

confidence: 99%

Section: Comparing the Results With Other Published Studiesmentioning

confidence: 99%

Section: The Risk Of Developing Neoplasms During or After Gh Treatmenmentioning

confidence: 99%

Section: The Risk Of Developing Neoplasms During or After Gh Treatmenmentioning

confidence: 99%

See 3 more Smart Citations

Safety of GH after treatment for childhood cancer

Santen

2020

European Journal of Endocrinology

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Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

et al. 2021

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Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

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Pharmacogenomics applied to recombinant human growth hormone responses in children with short stature

Stevens

Perchard

Garner

et al. 2021

Rev Endocr Metab Disord

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We present current knowledge concerning the pharmacogenomics of growth hormone therapy in children with short stature. We consider the evidence now emerging for the polygenic nature of response to recombinant human growth hormone (r-hGH). These data are related predominantly to the use of transcriptomic data for prediction. The impact of the complex interactions of developmental phenotype over childhood on response to r-hGH are discussed. Finally, the issues that need to be addressed in order to develop a clinical test are described.

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Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study

Cited by 70 publications

References 27 publications

Safety of GH after treatment for childhood cancer

Safety of GH after treatment for childhood cancer

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

Pharmacogenomics applied to recombinant human growth hormone responses in children with short stature

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