Pediatric Brain Metastases

  • Radhika Sreeraman Kumar
  • Ronny L. RotondoEmail author


Brain metastases (BM) are a frequent occurrence in adults malignancies, with an expected 20–40% of adult patients expected to develop BM during their disease course. In comparison, the brain is a rare site of metastasis in pediatric extracranial solid tumors with an estimated incidence in the order of 1–10%. Nevertheless, with continuing improvements in systemic therapies leading to prolonged survival, the incidence of pediatric BM may rise. While there is a broad body of literature on the incidence and management of adult BM, including large randomized clinical trials, there is a paucity of published data on pediatric BM, limited primarily to small series and cases reports. Pediatric BM may present synchronously or more commonly in the setting of prior extracranial metastases, particularly to the lungs. Treatment has typically included surgical resection for isolated or symptomatic lesions, radiation therapy, chemotherapy, and possibly immunotherapy. Although the outcome for pediatric patients with BM is in general very poor, there are some reports of long-term survivors, suggesting that aggressive multimodal therapy may be warranted in a subset of patients.


Brain metastases Whole brain radiotherapy Stereotactic radiosurgery Sarcoma Germ cell tumor Neuroblastoma Renal tumor 


  1. Ahmed KA, Stallworth DG, Kim Y et al (2016) Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy. Ann Oncol 27(3):434–441CrossRefPubMedGoogle Scholar
  2. Aoyama H, Shirato H, Tago M et al (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295(21):2483–2491CrossRefPubMedGoogle Scholar
  3. Bouffet E, Doumi N, Thiesse P et al (1997) Brain metastases in children with solid tumors. Cancer 79(2):403–410CrossRefPubMedGoogle Scholar
  4. Brown PD, Brown CA, Pollock BE, Gorman DA, Foote RL (2008) Stereotactic radiosurgery for patients with “radioresistant” brain metastases. Neurosurgery 62(Suppl 2):790–801PubMedGoogle Scholar
  5. Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10(11):1037–1044CrossRefPubMedGoogle Scholar
  6. Croog VJ, Kramer K, Cheung NK et al (2010) Whole neuraxis irradiation to address central nervous system relapse in high-risk neuroblastoma. Int J Radiat Oncol Biol Phys 78(3):849–854CrossRefPubMedGoogle Scholar
  7. DuBois SG, Kalika Y, Lukens JN et al (1999) Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival. J Pediatr Hematol Oncol 21(3):181–189CrossRefPubMedGoogle Scholar
  8. Gobel U, Schneider DT, Teske C, Schonberger S, Calaminus G (2010) Brain metastases in children and adolescents with extracranial germ cell tumor - data of the MAHO/MAKEI-registry. Klin Padiatr 222(3):140–144CrossRefPubMedGoogle Scholar
  9. Goldman S, Echevarria ME, Fangusaro J (2007) Pediatric brain metastasis from extraneural malignancies: a review. In: Raizer JJ, Abrey LE (eds) Brain metastases, vol 1. Springer, New York, pp 143–168CrossRefGoogle Scholar
  10. Graus F, Walker RW, Allen JC (1983) Brain metastases in children. J Pediatr 103(4):558–561CrossRefPubMedGoogle Scholar
  11. Kano H, Yang HC, Kondziolka D et al (2010) Stereotactic radiosurgery for pediatric recurrent intracranial ependymomas. J Neurosurg Pediatr 6(5):417–423CrossRefPubMedGoogle Scholar
  12. Kebudi R, Ayan I, Gorgun O, Agaoglu FY, Vural S, Darendeliler E (2005) Brain metastasis in pediatric extracranial solid tumors: survey and literature review. J Neuro-Oncol 71(1):43–48CrossRefGoogle Scholar
  13. Kellie SJ, Hayes FA, Bowman L et al (1991) Primary extracranial neuroblastoma with central nervous system metastases characterization by clinicopathologic findings and neuroimaging. Cancer 68(9):1999–2006CrossRefPubMedGoogle Scholar
  14. Keshavarzi S, Meltzer H, Ben-Haim S et al (2009) Initial clinical experience with frameless optically guided stereotactic radiosurgery/radiotherapy in pediatric patients. Childs Nerv Syst 25(7):837–844CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kiess AP, Wolchok JD, Barker CA et al (2015) Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys 92(2):368–375CrossRefPubMedPubMedCentralGoogle Scholar
  16. Kramer K, Kushner B, Heller G, Cheung NK (2001) Neuroblastoma metastatic to the central nervous system. The Memorial Sloan-kettering Cancer Center Experience and a literature review. Cancer 91(8):1510–1519CrossRefPubMedGoogle Scholar
  17. Linskey ME, Andrews DW, Asher AL et al (2010) The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neuro-Oncol 96(1):45–68CrossRefGoogle Scholar
  18. Lowis SP, Foot A, Gerrard MP et al (1998) Central nervous system metastasis in Wilms’ tumor: a review of three consecutive United Kingdom trials. Cancer 83(9):2023–2029CrossRefPubMedGoogle Scholar
  19. Marina NM, Pratt CB, Shema SJ, Brooks T, Rao B, Meyer WH (1993) Brain metastases in osteosarcoma. Report of a long-term survivor and review of the St. Jude Children’s Research Hospital experience. Cancer 71(11):3656–3660CrossRefPubMedGoogle Scholar
  20. Matthay KK, Brisse H, Couanet D et al (2003) Central nervous system metastases in neuroblastoma: radiologic, clinical, and biologic features in 23 patients. Cancer 98(1):155–165CrossRefPubMedGoogle Scholar
  21. Nabavizadeh SA, Feygin T, Harding BN, Bilaniuk LT, Zimmerman RA, Vossough A (2014) Imaging findings of patients with metastatic neuroblastoma to the brain. Acad Radiol 21(3):329–337CrossRefPubMedGoogle Scholar
  22. Nayak L, Lee EQ, Wen PY (2012) Epidemiology of brain metastases. Curr Oncol Rep 14(1):48–54CrossRefPubMedGoogle Scholar
  23. Niazi TN, Forester C, Afify Z, Riva-Cambrin J (2009) Osteosarcoma presenting as hemorrhagic cerebellar metastasis. Childs Nerv Syst 25(12):1643–1647CrossRefPubMedGoogle Scholar
  24. Osawa S, Kumabe T, Saito R et al (2011) Infratentorial brain metastases of pediatric non-epithelial malignant tumors: three case reports. Brain Tumor Pathol 28(2):167–174CrossRefPubMedGoogle Scholar
  25. Parasuraman S, Langston J, Rao BN et al (1999) Brain metastases in pediatric Ewing sarcoma and rhabdomyosarcoma: the St. Jude Children’s Research Hospital experience. J Pediatr Hematol Oncol 21(5):370–377CrossRefPubMedGoogle Scholar
  26. Paulino AC, Nguyen TX, Barker JL (2003) Brain metastasis in children with sarcoma, neuroblastoma, and Wilms’ tumor. Int J Radiat Oncol Biol Phys 57(1):177–183CrossRefPubMedGoogle Scholar
  27. Porto L, Jarisch A, Zanella F, Du Mesnil R, Kieslich M, Schwabe D (2010) The role of magnetic resonance imaging in children with hematogenous brain metastases from primary solid tumors. Pediatr Hematol Oncol 27(2):103–111CrossRefPubMedGoogle Scholar
  28. Radulescu VC, Gerrard M, Moertel C et al (2008) Treatment of recurrent clear cell sarcoma of the kidney with brain metastasis. Pediatr Blood Cancer 50(2):246–249CrossRefPubMedGoogle Scholar
  29. Rai P, Feusner JH (2016) Cerebral metastasis of hepatoblastoma: a review. J Pediatr Hematol Oncol 38(4):279–282CrossRefPubMedGoogle Scholar
  30. Robertson PL, Muraszko KM, Axtell RA (1997) Hepatoblastoma metastatic to brain: prolonged survival after multiple surgical resections of a solitary brain lesion. J Pediatr Hematol Oncol 19(2):168–171CrossRefPubMedGoogle Scholar
  31. Rodriguez-Galindo C, Pappo AS, Kaste SC et al (1997) Brain metastases in children with melanoma. Cancer 79(12):2440–2445CrossRefPubMedGoogle Scholar
  32. Sahgal A, Aoyama H, Kocher M et al (2015) Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 91(4):710–717CrossRefPubMedGoogle Scholar
  33. Saran FHB, Baumert BG, Khoo VS, Adams EJ, Garré ML, Warrington AP, Brada M (2002) Stereotactically guided conformal radiotherapy for progressive low-grade gliomas of childhood. Int J Radiat Oncol Biol Phys 53(1):43–51CrossRefPubMedGoogle Scholar
  34. Selek U, Chang EL, Hassenbusch SJ III et al (2004) Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases. Int J Radiat Oncol Biol Phys 59(4):1097–1106CrossRefPubMedGoogle Scholar
  35. Sheehan JP, Sun MH, Kondziolka D, Flickinger J, Lunsford LD (2003) Radiosurgery in patients with renal cell carcinoma metastasis to the brain: long-term outcomes and prognostic factors influencing survival and local tumor control. J Neurosurg 98(2):342–349CrossRefPubMedGoogle Scholar
  36. Soon YY, Tham IW, Lim KH, Koh WY, Lu JJ (2014) Surgery or radiosurgery plus whole brain radiotherapy versus surgery or radiosurgery alone for brain metastases. Cochrane Database Syst Rev 3:CD009454Google Scholar
  37. Spunt SL, Walsh MF, Krasin MJ et al (2004) Brain metastases of malignant germ cell tumors in children and adolescents. Cancer 101(3):620–626CrossRefPubMedGoogle Scholar
  38. Stefanowicz J, Izycka-Swieszewska E, Szurowska E et al (2011) Brain metastases in paediatric patients: characteristics of a patient series and review of the literature. Folia Neuropathol 49(4):271–281PubMedGoogle Scholar
  39. Stinauer MA, Kavanagh BD, Schefter TE et al (2011) Stereotactic body radiation therapy for melanoma and renal cell carcinoma: impact of single fraction equivalent dose on local control. Radiat Oncol 6(34):34CrossRefPubMedPubMedCentralGoogle Scholar
  40. Suki D, Khoury Abdulla R, Ding M, Khatua S, Sawaya R (2014) Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center. J Neurosurg Pediatr 14(4):372–385CrossRefPubMedGoogle Scholar
  41. Sul J, Posner JB (2007) Brain metastases: epidemiology and patholophysiology. In: Raizer JJ, Abrey LE (eds) Brain metastases, vol 1. Springer, New York, pp 1–22Google Scholar
  42. Tomlinson GE, Breslow NE, Dome J et al (2005) Rhabdoid tumor of the kidney in the National Wilms’ Tumor Study: age at diagnosis as a prognostic factor. J Clin Oncol 23(30):7641–7645CrossRefPubMedGoogle Scholar
  43. van Dams R, Park HS, Alomari AK et al (2016) Adjuvant hypofractionated partial-brain radiation therapy for pediatric Ewing sarcoma brain metastases: case report. J Neurosurg Pediatr 17(4):434–438CrossRefPubMedGoogle Scholar
  44. Vannucci RC, Baten M (1974) Cerebral metastatic disease in childhood. Neurology 24(10):981–985CrossRefPubMedGoogle Scholar
  45. Wexler LH, DeLaney TF, Saris S, Horowitz ME (1993) Long-term survival after central nervous system relapse in a patient with osteosarcoma. Cancer 72(4):1203–1208CrossRefPubMedGoogle Scholar
  46. Wiens AL, Hattab EM (2014) The pathological spectrum of solid CNS metastases in the pediatric population. J Neurosurg Pediatr 14(2):129–135CrossRefPubMedGoogle Scholar
  47. Zhu J, Wang J, Zhen ZJ et al (2015) Brain metastasis in children with stage 4 neuroblastoma after multidisciplinary treatment. Chin J Cancer 34(11):531–537PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Radiation OncologyH. L. Moffitt Cancer CenterTampaUSA
  2. 2.Radiation Oncology ServicesRiverdaleUSA
  3. 3.Department of Radiation Oncology, University of Florida College of MedicineJacksonvilleUSA

Personalised recommendations