Skip to main content
SpringerLink
Log in

Pediatric Brain Tumors: Viewpoint—Chemotherapy

  • Chapter
Principles and Practice of Stereotactic Radiosurgery

  • 2548 Accesses

Abstract

Pediatric brain tumors encompass a heterogeneous group of diseases. For many tumors, such as low-grade glioma and standard-risk medulloblastoma, the long-term survival rate is high. Clinical investigation for these diseases in recent decades has focused on addressing late effects of therapy, in particular the neurocognitive effects of cranial radiation. Chemotherapy has been used effectively in many settings to delay radiation, to reduce radiation dose and volume, or to replace cranial irradiation entirely. For other tumors, diffuse intrinsic pontine glioma most notoriously, prognosis remains abysmal and currently available treatments are primarily palliative. Stereotactic radiosurgery (SRS) has advantages over other therapeutic modalities in certain settings and has a role in the management pediatric brain tumors. That role is limited, however, by the propensity of pediatric neural tumors to disseminate along cerebrospinal fluid (CSF) pathways or to infiltrate surrounding brain.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pollack IF. Multidisciplinary management of childhood brain tumors: a review of outcomes, recent advances, and challenges. J Neurosurg Pediatr. 2011;8(2):135–48.

    Article  PubMed  Google Scholar 

  2. Turner CD, Rey-Casserly C, Liptak CC, Chordas C. Late effects of therapy for pediatric brain tumor survivors. J Child Neurol. 2009; 24(11):1455–63.

    Article  PubMed  Google Scholar 

  3. Guruangan S, Dunkel IJ, Goldman S, Garvin JH, Rosenblum M, Boyett JM, et al. Myeloablative chemotherapy with autologous bone marrow rescue in young children with recurrent malignant brain tumors. J Clin Oncol. 1998;16(7):2486–93.

    CAS  PubMed  Google Scholar 

  4. Heideman RL, Douglass EC, Krance RA, Fontanesi J, Langston JA, Sanford RA, et al. High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas. J Clin Oncol. 1993;11(8):1458–65.

    CAS  PubMed  Google Scholar 

  5. Hall WA, Djalilian HR, Sperduto PW, Cho KH, Gerbi BJ, Gibbons JP, et al. Stereotactic radiosurgery for recurrent malignant gliomas. J Clin Oncol. 1995;13(7):1642–8.

    CAS  PubMed  Google Scholar 

  6. Baumann GS, Wara WM, Larson DA, Sneed PK, Gutin PH, Ciricillo SF, et al. Gamma knife radiosurgery in children. Pediatr Neurosurg. 1996;24(4):193–201.

    Article  CAS  PubMed  Google Scholar 

  7. Parsa CF, Givrad S. Juvenile pilocytic astrocytomas do not undergo spontaneous malignant transformation: grounds for designation as hamartomas. Br J Ophthalmol. 2008;92(1):40–6.

    Article  CAS  PubMed  Google Scholar 

  8. Marcus KJ, Goumnerova L, Billett AL, Lavally B, Scott RM, Bishop K, et al. Stereotactic radiotherapy for localized low-grade gliomas in children: final results of a prospective trial. Int J Radiat Oncol Biol Phys. 2005;61(2):374–9.

    Article  PubMed  Google Scholar 

  9. Perilongo G. Considerations on the role of chemotherapy and modern radiotherapy in the treatment of childhood low grade glioma. J Neurooncol. 2005;75(3):301–7.

    Article  PubMed  Google Scholar 

  10. Ater JL, Zhou T, Holmes E, Mazewski CM, Booth TN, Freyer DR, et al. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30(21):2641–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22665535

  11. Scheinemann K, Bartels U, Tsangaris E, Hawkins C, Huang A, Dirks P, et al. Feasibility and efficacy of repeated chemotherapy for progressive pediatric low-grade gliomas. Pediatr Blood Cancer. 2011;57(1):84–8.

    Article  PubMed  Google Scholar 

  12. Sardi I, Bresci C, Schiavello E, Biassoni V, Fratoni V, Cardellicchio S, et al. Successful treatment with a low-dose cisplatin-etoposide regimen for patients with diencephalic syndrome. J Neurooncol. 2012;109(2):375–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22717669

  13. Gururangan S, Fisher MJ, Allen JC, Herndon 2nd JE, Quinn JA, Reardon DA, et al. Temozolomide in children with progressive low-grade glioma. Neuro Oncol. 2007;9(2):161–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Gururangan S, Cavazos CM, Ashley D, Herndon 2nd JE, Bruggers CS, Moghrabi A, et al. Phase II study of carboplatin in children with progressive low-grade gliomas. J Clin Oncol. 2002;20(13): 2951–8.

    Article  CAS  PubMed  Google Scholar 

  15. Bouffet E, Jakacki R, Goldman S, Hargrave D, Hawkins C, Shroff M, et al. Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol. 2012;30(12): 1358–63.

    Article  CAS  PubMed  Google Scholar 

  16. Somaza SC, Kondziolka D, Lunsford LD, Flickinger JC, Bissonette DJ, Albright AL. Early outcomes after stereotactic radiosurgery for growing pilocytic astrocytomas in children. Pediatr Neurosurg. 1996;25(3):109–15.

    Article  CAS  PubMed  Google Scholar 

  17. Grabb PA, Lunsford LD, Albright AL, Kondziolka D, Flickinger JC. Stereotactic radiosurgery for glial neoplasms of childhood. Neurosurgery. 1996;38(4):696–701; discussion 701–2.

    Article  CAS  PubMed  Google Scholar 

  18. Kida Y, Kobayashi T, Mori Y. Gamma knife radiosurgery for low-grade astrocytomas: results of long-term follow up. J Neurosurg. 2000;93 Suppl 3:42–6.

    PubMed  Google Scholar 

  19. Boëthius J, Ulfarsson E, Rähn T, Lippittz B. Gamma knife radiosurgery for pilocytic astrocytomas. J Neurosurg. 2002;97(5 Suppl): 677–80.

    PubMed  Google Scholar 

  20. Giller CA, Berger BD, Pistenmaa DA, Sklar F, Weprin B, Shapiro K, et al. Robotically guided radiosurgery for children. Pediatr Blood Cancer. 2005;45(3):304–10.

    Article  PubMed  Google Scholar 

  21. Lizarraga KJ, Gorgulho A, Lee SP, Rauscher G, Selch MT, DeSalles AAF. Stereotactic radiation therapy for progressive residual pilocytic astrocytomas. J Neurooncol. 2012;109(1):129–35.

    Article  PubMed  Google Scholar 

  22. Hallemeier CL, Pollock BE, Schomberg PJ, Link MJ, Brown PD, Stafford SL. Stereotactic radiosurgery for recurrent or unresectable pilocytic astrocytoma. Int J Radiat Oncol Biol Phys. 2012;83(1): 107–12.

    Article  PubMed  Google Scholar 

  23. Kano H, Niranjan A, Kondziolka D, Flickinger JC, Pollack IF, Jakacki RI, et al. Stereotactic radiosurgery for pilocytic astrocytomas part 2: outcomes in pediatric patients. J Neurooncol. 2009; 95(2):219–29.

    Article  PubMed  Google Scholar 

  24. Balasubramaniam A, Shannon P, Hodaie M, Laperriere N, Michaels H, Guha A. Glioblastoma multiforme after stereotactic radiotherapy for acoustic neuroma: case report and review of the literature. Neuro Oncol. 2007;9(4):447–53.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Guillamo J-S, Créange A, Kalifa C, Grill J, Rodriguez D, Doz F, et al. Prognostic factors of CNS tumours in neurofibromatosis 1 (NF1): a retrospective study of 104 patients. Brain. 2003;126(Pt 1): 152–60.

    Article  PubMed  Google Scholar 

  26. Kestle JR, Hoffman HJ, Mock AR. Moyamoya phenomenon after radiation for optic glioma. J Neurosurg. 1993;79(1):32–5.

    Article  CAS  PubMed  Google Scholar 

  27. Evans DGR, Birch JM, Ramsden RT, Sharif S, Baser ME. Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet. 2006;43(4):289–94.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Sharif S, Ferner R, Birch JM, Gillespie JE, Gattamaneni HR, Baser ME, et al. Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol. 2006;24(16):2570–5.

    Article  PubMed  Google Scholar 

  29. Ullrich NJ, Raja AI, Irons MB, Kieran MW, Goumnerova L. Brainstem lesions in neurofibromatosis type 1. Neurosurgery. 2007;61(4):762–6; discussion 766–7.

    Article  PubMed  Google Scholar 

  30. Jahraus CD, Tarbell NJ. Optic pathway gliomas. Pediatr Blood Cancer. 2006;46(5):586–96.

    Article  PubMed  Google Scholar 

  31. Davies SM. Therapy-related leukemia associated with alkylating agents. Med Pediatr Oncol. 2001;36(5):536–40.

    Article  CAS  PubMed  Google Scholar 

  32. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10): 987–96.

    Article  CAS  PubMed  Google Scholar 

  33. Cohen KJ, Pollack IF, Zhou T, Buxton A, Holmes EJ, Burger PC, et al. Temozolomide in the treatment of high-grade gliomas in children: a report from the Children’s Oncology Group. Neuro Oncol. 2011;13(3):317–23.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK. MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer. 2007;48(4):403–7.

    Article  PubMed  Google Scholar 

  35. Gururangan S, Chi SN, Young Poussaint T, Onar-Thomas A, Gilbertson RJ, Vajapeyam S, et al. Lack of efficacy of bevacizumab plus irinotecan in children with recurrent malignant glioma and diffuse brainstem glioma: a Pediatric Brain Tumor Consortium study. J Clin Oncol. 2010;28(18):3069–75.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Parekh C, Jubran R, Erdreich-Epstein A, Panigrahy A, Bluml S, Finlay J, et al. Treatment of children with recurrent high grade gliomas with a bevacizumab containing regimen. J Neurooncol. 2011; 103(3):673–80.

    Article  CAS  PubMed  Google Scholar 

  37. Shrieve DC, Alexander 3rd E, Wen PY, Fine HA, Kooy HM, Black PM, et al. Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme. Neurosurgery. 1995;36(2):275–82; discussion 282–4.

    Article  CAS  PubMed  Google Scholar 

  38. Song KS, Phi JH, Cho B-K, Wang K-C, Lee JY, Kim DG, et al. Long-term outcomes in children with glioblastoma. J Neurosurg Pediatr. 2010;6(2):145–9.

    Article  PubMed  Google Scholar 

  39. Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, et al. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993;328(24):1725–31.

    Article  CAS  PubMed  Google Scholar 

  40. Khatua S, Moore KR, Vats TS, Kestle JRW. Diffuse intrinsic pontine glioma-current status and future strategies. Childs Nerv Syst. 2011;27(9):1391–7.

    Article  PubMed  Google Scholar 

  41. Garvin Jr JH, Selch MT, Holmes E, Berger MS, Finlay JL, Flannery A, et al. Phase II study of pre-irradiation chemotherapy for childhood intracranial ependymoma. Children’s Cancer Group protocol 9942: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2012;59(7):1183–9.

    Article  PubMed  Google Scholar 

  42. Pollack IF, Gerszten PC, Martinez AJ, Lo KH, Shultz B, Albright AL, et al. Intracranial ependymomas of childhood: long-term outcome and prognostic factors. Neurosurgery. 1995;37(4):655–66; discussion 666–7.

    Article  CAS  PubMed  Google Scholar 

  43. Horn B, Heideman R, Geyer R, Pollack I, Packer R, Goldwein J, et al. A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol. 1999;21(3):203–11.

    Article  CAS  PubMed  Google Scholar 

  44. Oya N, Shibamoto Y, Nagata Y, Negoro Y, Hiraoka M. Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure. J Neurooncol. 2002;56(1):87–94.

    Article  PubMed  Google Scholar 

  45. Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA. Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol. 2009;10(3):258–66.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Agaoglu FY, Ayan I, Dizdar Y, Kebudi R, Gorgun O, Darendeliler E. Ependymal tumors in childhood. Pediatr Blood Cancer. 2005; 45(3):298–303.

    Article  PubMed  Google Scholar 

  47. Ghia AJ, Mahajan A, Allen PK, Armstrong TS, Lang Jr FF, Gilbert MR, et al. Supratentorial gross-totally resected non-anaplastic ependymoma: population based patterns of care and outcomes analysis. J Neurooncol. 2013;115(3):513–20.

    Article  PubMed  Google Scholar 

  48. Aizer AA, Ancukiewicz M, Nguyen PL, Macdonald SM, Yock TI, Tarbell NJ, et al. Natural history and role of radiation in patients with supratentorial and infratentorial WHO grade II ependymomas: results from a population-based study. J Neurooncol. 2013;115(3): 411–9.

    Article  PubMed  Google Scholar 

  49. Evans AE, Anderson JR, Lefkowitz-Boudreaux IB, Finlay JL. Adjuvant chemotherapy of childhood posterior fossa ependymoma: cranio-spinal irradiation with or without adjuvant CCNU, vincristine, and prednisone: a Childrens Cancer Group study. Med Pediatr Oncol. 1996;27(1):8–14.

    Article  CAS  PubMed  Google Scholar 

  50. Geyer JR, Zeltzer PM, Boyett JM, Rorke LB, Stanley P, Albright AL, et al. Survival of infants with primitive neuroectodermal tumors or malignant ependymomas of the CNS treated with eight drugs in 1 day: a report from the Childrens Cancer Group. J Clin Oncol. 1994;12(8):1607–15.

    CAS  PubMed  Google Scholar 

  51. Zacharoulis S, Levy A, Chi SN, Gardner S, Rosenblum M, Miller DC, et al. Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer. 2007;49(1):34–40.

    Article  PubMed  Google Scholar 

  52. Massimino M, Gandola L, Barra S, Giangaspero F, Casali C, Potepan P, et al. Infant ependymoma in a 10-year AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) experience with omitted or deferred radiotherapy. Int J Radiat Oncol Biol Phys. 2011;80(3):807–14.

    Article  PubMed  Google Scholar 

  53. Grundy RG, Wilne SA, Weston CL, Robinson K, Lashford LS, Ironside J, et al. Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study. Lancet Oncol. 2007;8(8):696–705.

    Article  PubMed  Google Scholar 

  54. Aggarwal R, Yeung D, Kumar P, Muhlbauer M, Kun LE. Efficacy and feasibility of stereotactic radiosurgery in the primary management of unfavorable pediatric ependymoma. Radiother Oncol. 1997;43(3):269–73.

    Article  CAS  PubMed  Google Scholar 

  55. Vaidya K, Smee R, Williams JR. Prognostic factors and treatment options for paediatric ependymomas. J Clin Neurosci. 2012;19(9): 1228–35.

    Article  CAS  PubMed  Google Scholar 

  56. Stauder MC, Ni Laack N, Ahmed KA, Link MJ, Schomberg PJ, Pollock BE. Stereotactic radiosurgery for patients with recurrent intracranial ependymomas. J Neurooncol. 2012;108(3):507–12.

    Article  PubMed  Google Scholar 

  57. Kano H, Yang H, Kondziolka D, Niranjan A, Arai Y, Flickinger JC, et al. Stereotactic radiosurgery for pediatric recurrent intracranial ependymomas. J Neurosurg Pediatr. 2010;6(5):417–23.

    Article  PubMed  Google Scholar 

  58. Gajjar A, Packer RJ, Foreman NK, Cohen K, Haas-Kogan D, Merchant TE. Children’s Oncology Group’s 2013 blueprint for research: central nervous system tumors. Pediatr Blood Cancer. 2013;60(6):1022–6.

    Article  PubMed Central  PubMed  Google Scholar 

  59. Padovani L, André N, Gentet JC, Muracciole X. Medulloblastoma. Eur J Cancer. 2011;47 Suppl 3:S338.

    Article  PubMed  Google Scholar 

  60. Chi SN, Gardner SL, Levy AS, Knopp EA, Miller DC, Wisoff JH, et al. Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma. J Clin Oncol. 2004;22(24):4881–7.

    Article  CAS  PubMed  Google Scholar 

  61. Dhall G, Grodman H, Ji L, Sands S, Gardner S, Dunkel IJ, et al. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols. Pediatr Blood Cancer. 2008; 50(6):1169–75.

    Article  PubMed  Google Scholar 

  62. Rutkowski S, Gerber NU, von Hoff K, Gnekow A, Bode U, Graf N, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. Neuro Oncol. 2009; 11(2):201–10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Chi SN, Zimmerman MA, Yao X, Cohen KJ, Burger P, Biegel JA, et al. Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol. 2009;27(3):385–9.

    Article  PubMed Central  PubMed  Google Scholar 

  64. Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M. Pre-radiation chemotherapy with response-based radiation therapy in children with central nervous system germ cell tumors: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2007;48(3):285–91.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Da Silva NS, Cappellano AM, Diez B, Cavalheiro S, Gardner S, Wisoff J, et al. Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study. Pediatr Blood Cancer. 2010;54(3):377–83.

    Article  PubMed  Google Scholar 

  66. Yoo KH, Lee SH, Lee J, Sung KW, Jung HL, Koo HH, et al. Improved outcome of central nervous system germ cell tumors: implications for the role of risk-adapted intensive chemotherapy. J Korean Med Sci. 2010;25(3):458–65.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Bouffet E. The role of myeloablative chemotherapy with autologous hematopoietic cell rescue in central nervous system germ cell tumors. Pediatr Blood Cancer. 2010;54(4):644–6.

    Article  PubMed  Google Scholar 

  68. Zissiadis Y, Dutton S, Kieran M, Goumnerova L, Scott RM, Kooy HM, et al. Stereotactic radiotherapy for pediatric intracranial germ cell tumors. Int J Radiat Oncol Biol Phys. 2001;51(1): 108–12.

    Article  CAS  PubMed  Google Scholar 

  69. Malone K, Croke J, Malone C, Malone S. Successful salvage using combined radiation and ABMT for patients with recurrent CNS NGGCT following failed initial transplant. BMJ Case Rep. 2012.

    Google Scholar 

  70. Tavangar SM, Larijani B, Mahta A, Hosseini SMA, Mehrazine M, Bandarian F. Craniopharyngioma: a clinicopathological study of 141 cases. Endocr Pathol. 2004;15(4):339–44.

    Article  PubMed  Google Scholar 

  71. Kobayashi T, Mori Y, Tsugawa T, Hashizume C, Takahashi H. Prognostic factors for tumor recurrence after gamma knife radiosurgery of partially resected and recurrent craniopharyngiomas. Nagoya J Med Sci. 2012;74(1–2):141–7.

    PubMed  Google Scholar 

  72. Niranjan A, Kano H, Mathieu D, Kondziolka D, Flickinger JC, Lunsford LD. Radiosurgery for craniopharyngioma. Int J Radiat Oncol Biol Phys. 2010;78(1):64–71.

    Article  PubMed  Google Scholar 

  73. Hasegawa T, Kobayashi T, Kida Y. Tolerance of the optic apparatus in single-fraction irradiation using stereotactic radiosurgery: evaluation in 100 patients with craniopharyngioma. Neurosurgery. 2010;66(4):688–94; discussion 694–5.

    Article  PubMed  Google Scholar 

  74. Yeung JT, Pollack IF, Panigrahy A, Jakacki RI. Pegylated interferon-α-2b for children with recurrent craniopharyngioma. J Neurosurg Pediatr. 2012;10(6):498–503.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, 4650 W. Sunset Blvd, MS #54, Los Angeles, CA, 90027, USA

    Nathan J. Robison M.D.

Authors
  1. Nathan J. Robison M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nathan J. Robison M.D. .

Editor information

Editors and Affiliations

  1. Department of Neurosurgery, SUNY Upstate Medical University, Syracuse, USA

    Lawrence S. Chin

  2. Dept. of Radiation Oncology, Univ. of Maryland School of Medicine, Baltimore, Maryland, USA

    William F. Regine

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Robison, N.J. (2015). Pediatric Brain Tumors: Viewpoint—Chemotherapy. In: Chin, L., Regine, W. (eds) Principles and Practice of Stereotactic Radiosurgery. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8363-2_33

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-8363-2_33

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-8362-5

  • Online ISBN: 978-1-4614-8363-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation