Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: A systematic review

Mulder, Renée L.; Kremer, Leontien C.M.; Santen, Hanneke M. van; Ket, Jan Lucas; Trotsenburg, A.S. Paul van; Koning, Caro C.E.; Meeteren, Antoinette Y.N. Schouten-van; Caron, Huib N.; Neggers, Sebastian J.C.M.M.; Dalen, Elvira C. van

doi:10.1016/j.ctrv.2009.06.004

« Previous Next »Cancer Treatment Reviews
Volume 35, Issue 7 , Pages 616-632, November 2009

Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: A systematic review

Renée L. Mulder
- Department of Paediatric Oncology, Emma Children’s Hospital/Academic Medical Center, F8 Noord, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
- Corresponding author. Tel.: +31 20 5666370; fax: +31 20 6912231.
Leontien C.M. Kremer
- Department of Paediatric Oncology, Emma Children’s Hospital/Academic Medical Center, F8 Noord, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
Hanneke M. van Santen
- Department of Paediatric Endocrinology, Emma Children’s Hospital/Academic Medical Center, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
Jan Lucas Ket
- Department of Paediatrics, Waterlandziekenhuis, P.O. Box 250, 1440 AG Purmerend, The Netherlands
A.S. Paul van Trotsenburg
- Department of Paediatric Endocrinology, Emma Children’s Hospital/Academic Medical Center, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands
Caro C.E. Koning
- Department of Radiation Oncology, Academic Medical Center, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
Antoinette Y.N. Schouten-van Meeteren
- Department of Paediatric Oncology, Emma Children’s Hospital/Academic Medical Center, F8 Noord, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
Huib N. Caron
- Department of Paediatric Oncology, Emma Children’s Hospital/Academic Medical Center, F8 Noord, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands
Sebastian J.C.M.M. Neggers
- Department of Paediatric Oncology/Haematology, Erasmus University Medical Center/Sophia Children’s Hospital & Department of Medicine, Section Endocrinology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
Elvira C. van Dalen
- Department of Paediatric Oncology, Emma Children’s Hospital/Academic Medical Center, F8 Noord, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands

Received 27 February 2009; received in revised form 11 June 2009; accepted 15 June 2009. published online 29 July 2009.

Summary

Background

Growth hormone deficiency (GHD) is usually the first and most frequent endocrine problem occurring after cranial radiotherapy (CRT). The aim of this systematic review was to evaluate the existing evidence of the prevalence and risk factors of radiation-induced GHD in childhood cancer survivors.

Methods

MEDLINE, EMBASE and CENTRAL were searched for studies reporting on radiation-induced GHD in childhood cancer survivors. Information about study characteristics, prevalence and risk factors was abstracted and the quality of each study was assessed. A meta-regression analysis was performed.

Results

The prevalence of radiation-induced GHD was estimated in 33 studies. Most studies had methodological limitations. The prevalence varied considerably between 0% and 90.9%. Selecting only the studies with adequate peak GH cut-off limits (<5μg/L) resulted in 3 studies. In these studies the prevalence ranged from 29.0% to 39.1%, with a pooled prevalence of 35.6%. Higher CRT dose and longer follow-up time have been suggested to be the main risk factors of GHD by studies included in this review. The meta-regression analysis showed that the wide variation in the prevalence of GHD could be explained by differences in maximal CRT dose.

Conclusions

GHD is a frequent consequence after CRT in childhood cancer survivors. The prevalence of radiation-induced GHD ranged from 29.0% to 39.1% when selecting only studies with adequate peak GH cut-off limits. Higher CRT dose and longer follow-up time are the main risk factors. More well-designed studies are needed to accurately estimate the prevalence of GHD and to define the exact CRT threshold dose.

Keywords: Growth hormone deficiency, Childhood cancer survivors, Cranial radiotherapy, Systematic review