title: Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma.
abstract: OBJECTIVE
  Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure.
  
  
  METHODS
  Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990-2010 and alive ≥ 2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts.
  
  
  RESULTS
  Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79-2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60-2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19-1.90).
  
  
  CONCLUSIONS
  Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population.
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Center, Amsterdam, The Netherlands; Department of Pediatric Endocrinology, Wilhelmina Children's Hospital University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: s.c.clement@amc.uva.nl.
authors.forename: S C
authors.initials: SC
authors.lastname: Clement
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: Schoot
authors.affiliation: Department of Pediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
authors.forename: O
authors.initials: O
authors.lastname: Slater
authors.affiliation: Children and Young People's Department, Royal Marsden Hospital, Sutton, United Kingdom.
authors.forename: J C
authors.initials: JC
authors.lastname: Chisholm
authors.affiliation: Craniofacial Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Abela
authors.affiliation: Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Oral and Maxillofacial surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: A J M
authors.initials: AJM
authors.lastname: Balm
authors.affiliation: Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Oral and Maxillofacial surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: van den Brekel
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: W B
authors.initials: WB
authors.lastname: Breunis
authors.affiliation: Department of Oncology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: Y C
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Davila Fajardo
authors.affiliation: Craniofacial Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: Dunaway
authors.affiliation: Department of Ophthalmology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Gajdosova
authors.affiliation: Department of Oncology, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
authors.forename: M N
authors.initials: MN
authors.lastname: Gaze
authors.affiliation: Department of Otorhinolaryngology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Otorhinolaryngology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
authors.forename: B
authors.initials: B
authors.lastname: Hartley
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: L C M
authors.initials: LCM
authors.lastname: Kremer
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Lennep
authors.affiliation: Department of Pediatric Oncology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
authors.forename: G A
authors.initials: GA
authors.lastname: Levitt
authors.affiliation: Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
authors.forename: H C
authors.initials: HC
authors.lastname: Mandeville
authors.affiliation: Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: B R
authors.initials: BR
authors.lastname: Pieters
authors.affiliation: Orbital center, Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Saeed
authors.affiliation: Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Oral and Maxillofacial surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: L E
authors.initials: LE
authors.lastname: Smeele
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: S D
authors.initials: SD
authors.lastname: Strackee
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Ronckers
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: H N
authors.initials: HN
authors.lastname: Caron
authors.affiliation: Department of Pediatric Endocrinology, Wilhelmina Children's Hospital University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: van Santen
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J H M
authors.initials: JHM
authors.lastname: Merks
mesh_terms: D000293:Adolescent; D041923:Adolescent Development; D000328:Adult; D000367:Age Factors; D001918:Brachytherapy / Q000009:adverse effects*; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008131:London / Q000453:epidemiology; D008297:Male; D015999:Multivariate Analysis; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010900:Pituitary Diseases / Q000175:diagnosis / Q000453:epidemiology*; D010901:Pituitary Function Tests; D015995:Prevalence; D011832:Radiation Injuries / Q000175:diagnosis / Q000453:epidemiology*; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012208:Rhabdomyosarcoma / Q000532:radiotherapy* / Q000601:surgery; D012307:Risk Factors; D017741:Survivors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
keywords: Adverse endocrine events; Brachytherapy; Head and neck; Paediatric oncology; Pituitary dysfunction; Radiotherapy; Rhabdomyosarcoma