title: Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single-Bone CNS-Risk Lesions: A Multi-Institutional Retrospective Study.
abstract: BACKGROUND
  Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or radiotherapy changes outcomes in these patients.
  
  
  METHODS
  Ten pediatric institutions across North America and Europe contributed data of their patients with LCH and single-bone CNS-risk lesions. Clinical information on age, sex, specific craniofacial site involvement, and intracranial extension at diagnosis, therapy, and disease course was collected for all eligible patients.
  
  
  RESULTS
  The final analysis included 93 eligible children who were either treated with systemic therapy (chemotherapy, chemo-radiotherapy, or radiotherapy) or local therapy (biopsy, curettage, and/or intralesional steroids). Fifty-nine patients had systemic and 34 had local therapy. The 5-year event-free survival (EFS) and overall survival (OS) were 80 ± 5% and 98 ± 2% in the systemic therapy group versus 85 ± 6% and 95 ± 5% in the local therapy group. There was no statistically significant difference between either group with regard to EFS (P = 0.26) and OS (P = 0.78). On multivariable analysis, there was no significant difference among the two treatment groups after adjusting for site and intracranial soft tissue extension, nor any trend favoring systemic therapy (HR = 2.26, 95% CI = 0.77-6.70; P = 0.14).
  
  
  CONCLUSIONS
  Systemic therapy may not reduce the risk of recurrence or late sequelae in children with LCH and single-bone CNS-risk lesions as compared to local treatment.
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Deepak
authors.initials: D
authors.lastname: Chellapandian
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Furqan
authors.initials: F
authors.lastname: Shaikh
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Cor
authors.initials: C
authors.lastname: van den Bos
authors.affiliation: Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Gino R
authors.initials: GR
authors.lastname: Somers
authors.affiliation: Servicio de Pediatria, Bio Cruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain.|Departamento de Pediatria, Universidad del Pais Vasco UPV/EHU, Vizcaya, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Astigarraga
authors.affiliation: Children's Hospital of Los Angeles, Los Angeles, California.
authors.forename: Rima
authors.initials: R
authors.lastname: Jubran
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Barbara
authors.initials: B
authors.lastname: Degar
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Carret
authors.affiliation: Division of Hematology/Oncology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Mandel
authors.affiliation: Department of Pediatrics, University of Alberta, Stollery Children's Hospital, Edmonton, Alberta, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Belletrutti
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Dix
authors.affiliation: Leicester Children's Hospital, Leicester, UK.
authors.forename: Johannes
authors.initials: J
authors.lastname: Visser
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Nour
authors.initials: N
authors.lastname: Abuhadra
authors.affiliation: Keck School of Medicine of the University of Southern California, Los Angeles, California.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Chang
authors.affiliation: Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Barret
authors.initials: B
authors.lastname: Rollins
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Whitlock
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Oussama
authors.initials: O
authors.lastname: Abla
mesh_terms: D001847:Bone Diseases / Q000401:mortality* / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006646:Histiocytosis, Langerhans-Cell / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D007223:Infant; D008297:Male; D019636:Neurodegenerative Diseases / Q000401:mortality* / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate
keywords: CNS neurodegeneration; Langerhans cell histiocytosis; chemotherapy; diabetes insipidus; disease recurrence; radiotherapy