Risk Factors for Small Adult Height in Childhood Cancer Survivors

Abstract

BACKGROUND: Between 10-20% of childhood cancer survivors (CCS) suffer impaired growth leading to small adult height (SAH). Our study aimed to quantify risk factors for SAH or growth hormone (GH) deficiency among CCS. METHODS: The FCCSS holds data on 7670 cancers survivors treated before 2001. We analyzed self-questionnaire data from 2965 CCS with clinical, chemo/radiotherapy data from medical records. SAH was defined as an adult height <2 Standard Deviation Scores (SDS) of control values obtained from a French population health study. RESULTS: After exclusion of the 189 CCS treated with GH, 9.2% (254/2776) had a SAH. Being young at the time of cancer treatment (RR 0.91 [95% CI, 0.88-0.95], by year of age), small height at diagnosis ( 40 Gy RR 19.48 [95%CI, 8.73-43.48]), having received busulfan (RR 4.53 [95%CI, 2.10- 9.77]), or more than 300 mg/m² of lomustine ([300-600]mg/m² RR 4.21 [95%CI, 1.61-11.01], >600mg/m² RR 9.12 [95%CI, 2.75-30.24]) were all independent risk factors for SAH. Irradiation of seven or more vertebrae (>15 Gy on >90% of their volume) without pituitary irradiation increased the RR of SAH by 4.62 [95%CI, 2.77-7.72]. If patients had also received pituitary irradiation, this increased the RR by an additional factor of 1.3 to 2.4. CONCLUSION: CCS are at high risk of SAH. Any CCS who has been treated with radiotherapy, busulfan, or lomustine should be closely monitored for growth, puberty onset, and potential pituitary deficiency. FUNDING STATEMENT: This work was supported by the French Society of Childhood Cancer (SFCE), the PAIR Research Program “START - INCa-ARC-Ligue_11902, the PAIR Research Program “Mr Robot” – INCa-ARCLIGUE_11909, the Electricite de France (EDF), the Pfizer Foundation for childhood and adolescent health, the Ligue Nationale Contre le Cancer (LNCC), the Institut de Recherche en Sante Publique (IRESP), and the French “Agence Nationale Pour la Recherche Scientifique” (Hope-Epi Project). DECLARATION OF INTERESTS: All authors declared to have no conflict of interest with this study. ETHICS APPROVAL STATEMENT: The study has been approved by the French Data Protection Authority (CNIL) and the ethics committee of the National Institute of Medical Research and Health (INSERM).