Deepak Chellapandian1, Furqan Shaikh1, Cor van den Bos2, Gino R Somers3, Itziar Astigarraga4,5, Rima Jubran6, Barbara Degar7, Anne-Sophie Carret8, Karen Mandel9, Mark Belletrutti10, David Dix11, Johannes Visser12, Nour Abuhadra1, Tiffany Chang13, Barret Rollins14, James Whitlock1, Sheila Weitzman1, Oussama Abla1. 1. Department of Pediatrics, Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada. 2. Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands. 3. Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada. 4. Servicio de Pediatria, Bio Cruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain. 5. Departamento de Pediatria, Universidad del Pais Vasco UPV/EHU, Vizcaya, Spain. 6. Children's Hospital of Los Angeles, Los Angeles, California. 7. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 8. Division of Hematology-Oncology, Department of Pediatrics, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada. 9. Division of Hematology/Oncology, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada. 10. Department of Pediatrics, University of Alberta, Stollery Children's Hospital, Edmonton, Alberta, Canada. 11. Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada. 12. Leicester Children's Hospital, Leicester, UK. 13. Keck School of Medicine of the University of Southern California, Los Angeles, California. 14. Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts.
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). CONCLUSION: 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.
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). CONCLUSION: 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.