Risk Factors for Small Adult Height in Childhood Cancer Survivors

J Clin Oncol. 2020 Jun 1;38(16):1785-1796. doi: 10.1200/JCO.19.02361. Epub 2020 Mar 20.

Abstract

Purpose: Between 10% and 20% of childhood cancer survivors (CCS) experience impaired growth, leading to small adult height (SAH). Our study aimed to quantify risk factors for SAH or growth hormone deficiency among CCS.

Methods: The French CCS Study holds data on 7,670 cancer survivors treated before 2001. We analyzed self-administered questionnaire data from 2,965 CCS with clinical, chemo/radiotherapy data from medical records. SAH was defined as an adult height ≤ 2 standard deviation scores of control values obtained from a French population health study.

Results: After exclusion of 189 CCS treated with growth hormone, 9.2% (254 of 2,776) had a SAH. Being young at the time of cancer treatment (relative risk [RR], 0.91 [95% CI, 0.88 to 0.95] by year of age), small height at diagnosis (≤ 2 standard deviation scores; RR, 6.74 [95% CI, 4.61 to 9.86]), pituitary irradiation (5-20 Gy: RR, 4.24 [95% CI, 1.98 to 9.06]; 20-40 Gy: RR, 10.16 [95% CI, 5.18 to 19.94]; and ≥ 40 Gy: RR, 19.48 [95% CI, 8.73 to 43.48]), having received busulfan (RR, 4.53 [95% CI, 2.10 to 9.77]), or > 300 mg/m2 of lomustine (300-600 mg/m2: RR, 4.21 [95% CI, 1.61 to 11.01] and ≥ 600 mg/m2: RR, 9.12 [95% CI, 2.75 to 30.24]) were all independent risk factors for SAH. Irradiation of ≥ 7 vertebrae (≥ 15 Gy on ≥ 90% of their volume) without pituitary irradiation increased the RR of SAH by 4.62 (95% CI, 2.77 to 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 a high risk of SAH. CCS treated with radiotherapy, busulfan, or lomustine should be closely monitored for growth, puberty onset, and potential pituitary deficiency.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Body Height*
  • Busulfan / adverse effects*
  • Cancer Survivors*
  • Child
  • Child, Preschool
  • Female
  • France / epidemiology
  • Growth Disorders / diagnosis
  • Growth Disorders / drug therapy
  • Growth Disorders / epidemiology*
  • Growth Disorders / physiopathology
  • Hormone Replacement Therapy
  • Human Growth Hormone / blood
  • Human Growth Hormone / deficiency*
  • Human Growth Hormone / therapeutic use
  • Humans
  • Lomustine / adverse effects*
  • Male
  • Neoplasms / epidemiology
  • Neoplasms / therapy*
  • Puberty
  • Radiation Injuries / diagnosis
  • Radiation Injuries / drug therapy
  • Radiation Injuries / epidemiology*
  • Radiation Injuries / physiopathology
  • Radiotherapy / adverse effects
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Human Growth Hormone
  • Lomustine
  • Busulfan