Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy

Abstract

Background: Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH.

Procedure: Retrospective cohort study (1980-2010) of 119 survivors treated with rhGH for irradiation-induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD.

Results: Median survivor follow-up since rhGH initiation was 4.8 (range 0.2-18.3) years. SCFE was diagnosed in 10 subjects post-TBI and none after CI (P < 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211-fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency.

Conclusions: The markedly greater SCFE incidence rate in childhood cancer survivors with TBI-associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE.

Keywords: SCFE; childhood cancer survivors; cranial irradiation; growth hormone; total body irradiation.

Fig. 1

Antero-posterior (AP) (A) and frog-leg lateral radiographs (B) showing left lateral and posterior (valgus) slip of the capital femoral epiphysis in a patient on rhGH therapy after total body irradiation (TBI). C: Pre-operative AP radiograph of the pelvis showing bilateral valgus slipped capital femoral epiphysis (SCFE) in a childhood cancer survivor on rhGH after TBI. D: Post-operative AP radiograph of the same patient demonstrating screw fixation of the bilateral SCFE.