Skip to main content

Advertisement

SpringerLink
Log in

Available Therapies for Patients with Neurofibromatosis-Related Nervous System Tumors

  • Neuro-oncology (GJ Lesser, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Though the majority of nervous system tumors are sporadic, several clinically relevant genetic syndromes are associated with a predisposition to tumors of the central and peripheral nervous system including neurofibromatosis type 1 (NF1), type 2 (NF2), and schwannomatosis (SWN). These represent prototypical tumor suppressor syndromes where loss of a tumor suppressor gene-protein impairs the cell’s ability to regulate cell proliferation. While clinical manifestations vary widely for each of these syndromes, tumors arising in the peripheral nerve sheath are a unifying feature. Clinical clues should prompt the clinician to recognize the underlying genetic syndrome and screen for associated tumors including, among others, plexiform neurofibromas and gliomas in NF1 and vestibular schwannomas, meningiomas, and spinal ependymomas in NF2. Improvements in mechanistic understanding of how the genetic mutations that underlie these syndromes contribute to tumor formation have led to new advances in targeted therapies. MEK inhibitors have shown promise for treating progressive plexiform neurofibromas in NF1. Bevacizumab has been shown to improve hearing and treat vestibular schwannomas in NF2. This article reviews the currently available data on management of tumors associated with these three syndromes.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Lammert M, Friedman JM, Kluwe L, Mautner VF. Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol. 2005;141(1):71–4.

    Article  PubMed  Google Scholar 

  2. Evans DG, Bowers NL, Tobi S, Hartley C, Wallace AJ, King AT, et al. Schwannomatosis: a genetic and epidemiological study. J Neurol Neurosurg Psychiatry. 2018;89:1–5. https://doi.org/10.1136/jnnp-2018-318538.

    Article  Google Scholar 

  3. Hino O, Kobayashi T. Mourning Dr. Alfred G. Knudson: the two-hit hypothesis, tumor suppressor genes, and the tuberous sclerosis complex. Cancer Sci. 2017;108(1):5–11. https://doi.org/10.1111/cas.13116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Radtke HB, Sebold CD, Allison C, Haidle JL, Schneider G. Neurofibromatosis type 1 in genetic counseling practice: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2007;16:387–407. https://doi.org/10.1007/s10897-007-9101-8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yap Y-S, McPherson JR, Ong C-K, et al. The NF1 gene revisited - from bench to bedside. Oncotarget. 2014;5(15):5873–92. https://doi.org/10.18632/oncotarget.2194.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44(2):81–8. https://doi.org/10.1136/jmg.2006.045906.

    Article  CAS  PubMed  Google Scholar 

  7. DeBella K, Szudek J, Friedman JM. Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children. Pediatrics. 2000;105(3 Pt 1):608–14.

    Article  CAS  PubMed  Google Scholar 

  8. Evans DGR. Neurofibromatosis type 2 (NF2): a clinical and molecular review. Orphanet J Rare Dis. 2009;4:16.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Elaimy AL, Mercurio AM. Convergence of VEGF and YAP/TAZ signaling: implications for angiogenesis and cancer biology. Sci Signal. 2018;11(552):eaau1165. https://doi.org/10.1126/scisignal.aau1165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. The Consensus Development Panel. National Institutes of Health consensus development conference statement on acoustic neuroma, December 11-13, 1991 The Consensus Development Panel. Arch Neurol. 1994;51(2):201–7.

    Article  Google Scholar 

  11. Merker VL, Esparza S, Smith MJ, Stemmer-Rachamimov A, Plotkin SR. Clinical features of schwannomatosis: a retrospective analysis of 87 patients. Oncologist. 2012;17(10):1317–22. https://doi.org/10.1634/theoncologist.2012-0162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Karajannis MA, Legault G, Hagiwara M, Ballas MS, Brown K, Nusbaum AO, et al. Phase II trial of lapatinib in adult and pediatric patients with neurofibromatosis type 2 and progressive vestibular schwannomas. Neuro-Oncology. 2012;14(9):1163–70. https://doi.org/10.1093/neuonc/nos146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hulsebos TJM, Kenter S, Siebers-Renelt U, Hans V, Wesseling P, Flucke U. SMARCB1 involvement in the development of leiomyoma in a patient with schwannomatosis. Am J Surg Pathol. 2014;38(3):421–5. https://doi.org/10.1097/PAS.0000000000000110.

    Article  PubMed  Google Scholar 

  14. Bacci C, Sestini R, Provenzano A, Paganini I, Mancini I, Porfirio B, et al. Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1 mutation. Neurogenetics. 2010;11(1):73–80. https://doi.org/10.1007/s10048-009-0204-2.

    Article  CAS  PubMed  Google Scholar 

  15. Zhu Y, Ghosh P, Charnay P, Burns DK, Parada LF. Neurofibromas in NF1: Schwann cell origin and role of tumor environment. Science. 2002;296(5569):920–2. https://doi.org/10.1126/science.1068452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Widemann BC, Dombi E, Gillespie A, Wolters PL, Belasco J, Goldman S, et al. Phase 2 randomized, flexible crossover, double-blinded, placebo-controlled trial of the farnesyltransferase inhibitor tipifarnib in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas. Neuro-Oncology. 2014;16(5):707–18. https://doi.org/10.1093/neuonc/nou004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Widemann BC, Babovic-Vuksanovic D, Dombi E, Wolters PL, Goldman S, Martin S, et al. Phase II trial of pirfenidone in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas. Pediatr Blood Cancer. 2014;61(9):1598–602. https://doi.org/10.1002/pbc.25041.

    Article  CAS  PubMed  Google Scholar 

  18. Weiss B, Widemann BC, Wolters P, Dombi E, Vinks AA, Cantor A, et al. Sirolimus for non-progressive NF1-associated plexiform neurofibromas: an NF clinical trials consortium phase II study. Pediatr Blood Cancer. 2014;61(6):982–6. https://doi.org/10.1002/pbc.24873.

    Article  CAS  PubMed  Google Scholar 

  19. Weiss B, Widemann BC, Wolters P, Dombi E, Vinks A, Cantor A, et al. Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a neurofibromatosis Clinical Trials Consortium phase II study. Neuro-Oncology. 2015;17(4):596–603. https://doi.org/10.1093/neuonc/nou235.

    Article  CAS  PubMed  Google Scholar 

  20. Jakacki RI, Dombi E, Steinberg SM, Goldman S, Kieran MW, Ullrich NJ, et al. Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas. Neuro-Oncology. 2017;19(2):289–97. https://doi.org/10.1093/neuonc/now158.

    Article  CAS  PubMed  Google Scholar 

  21. Robertson KA, Nalepa G, Yang FC, Bowers DC, Ho CY, Hutchins GD, et al. Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial. Lancet Oncol. 2012;13(12):1218–24. https://doi.org/10.1016/S1470-2045(12)70414-X.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. •• Dombi E, Baldwin A, Marcus LJ, et al. Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas. N Engl J Med. 2016;375(26):2550–60. https://doi.org/10.1056/NEJMoa1605943 This study describes results of the phase 1 study of selumetinib for treating progressive plexiform neurofibromas in patients with NF1 demonstrating a dramatic 71% response rate.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. ••Gross AM, Wolters PL, Dombi E, et al. Selumetinib in children with inoperable plexiform neurofibromas. N Engl J Med. 2020. https://doi.org/10.1056/nejmoa1912735 This study describes results of the phase 2 study of selumetinib for treating symptomatic, inoperable plexiform neurofibromas in patients with NF1 demonstrating a 70% radiographic response and 68% clinical improvement rate.

  24. Cesaretti C, Melloni G, Quagliarini D, Fogliani R, Zaina B, Bedeschi MF, et al. Neurofibromatosis type 1 and pregnancy: maternal complications and attitudes about prenatal diagnosis. Am J Med Genet Part A. 2013;161(2):386–8. https://doi.org/10.1002/ajmg.a.35720.

    Article  Google Scholar 

  25. Terry AR, Barker FG, Leffert L, Bateman BT, Souter I, Plotkin SR. Neurofibromatosis type 1 and pregnancy complications: a population-based study. Am J Obstet Gynecol. 2013;209(1):46.e1–8. https://doi.org/10.1016/j.ajog.2013.03.029.

    Article  Google Scholar 

  26. Schnabel C, Jett K, Friedman JM, Frieling I, Kruse HP, Mautner V. Effect of vitamin D3 treatment on bone density in neurofibromatosis 1 patients: a retrospective clinical study. Jt Bone Spine. 2013;80(3):315–9. https://doi.org/10.1016/j.jbspin.2012.07.010.

    Article  CAS  Google Scholar 

  27. Stevenson DA, Viskochil DH, Carey JC, Sheng X, Murray M, Moyer-Mileur L, et al. Pediatric 25-hydroxyvitamin D concentrations in neurofibromatosis type 1. J Pediatr Endocrinol Metab. 2011;24(3–4):169–74. https://doi.org/10.1515/jpem.2011.092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Petramala L, Giustini S, Zinnamosca L, Marinelli C, Colangelo L, Cilenti G, et al. Bone mineral metabolism in patients with neurofibromatosis type 1 (von Recklingausen disease). Arch Dermatol Res. 2012;304(4):325–31. https://doi.org/10.1007/s00403-011-1191-3.

    Article  CAS  PubMed  Google Scholar 

  29. Lammert M, Friedman JM, Roth HJ, Friedrich RE, Kluwe L, Atkins D, et al. Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1. J Med Genet. 2006;43(10):810–3. https://doi.org/10.1136/jmg.2006.041095.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tovmassian D, Abdul Razak M, London K. The role of [18F]FDG-PET/CT in predicting malignant transformation of plexiform neurofibromas in neurofibromatosis-1. Int J Surg Oncol. 2016;2016:1–7. https://doi.org/10.1155/2016/6162182.

    Article  Google Scholar 

  31. Ahlawat S, Blakeley JO, Rodriguez FJ, Fayad LM. Imaging biomarkers for malignant peripheral nerve sheath tumors in neurofibromatosis type 1. Neurology. 2019;93(11):e1076–84. https://doi.org/10.1212/wnl.0000000000008092.

    Article  CAS  PubMed  Google Scholar 

  32. Taylor LA, Lewis VL. Neurofibromatosis type 1: Review of cutaneous and subcutaneous tumor treatment on quality of life. Plast Reconstr Surg - Glob Open. 2019;7(1):e1982. https://doi.org/10.1097/GOX.0000000000001982.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Slopis JM, Arevalo O, Bell CS, Hebert AA, Northrup H, Riascos RF, et al. Treatment of disfiguring cutaneous lesions in neurofibromatosis-1 with everolimus: a phase II, open-label, single-arm trial. Drugs R D. 2018;18(4):295–302. https://doi.org/10.1007/s40268-018-0248-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Riccardi VM. A controlled multiphase trial of ketotifen to minimize neurofibroma-associated pain and itching. Arch Dermatol. 1993;129(5):577–81 http://www.ncbi.nlm.nih.gov/pubmed/8481017. Accessed February 29, 2020.

    Article  CAS  PubMed  Google Scholar 

  35. Allaway RJ, Gosline SJC, La Rosa S, et al. Cutaneous neurofibromas in the genomics era: current understanding and open questions. Br J Cancer. 2018;118(12):1539–48. https://doi.org/10.1038/s41416-018-0073-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nakamura JL, Phong C, Pinarbasi E, Kogan SC, Vandenberg S, Horvai AE, et al. Dose-dependent effects of focal fractionated irradiation on secondary malignant neoplasms in Nf1 mutant mice. Cancer Res. 2011;71(1):106–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 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. https://doi.org/10.1200/JCO.2005.03.8349.

    Article  PubMed  Google Scholar 

  38. Papalia H, Audic F, Rivière GR, Verschuur A, André N. Quick and sustained clinical response to MEK inhibitor I in a NF1 patient with neurofibromas. Ecancermedicalscience. 2018;12:862. https://doi.org/10.3332/ecancer.2018.862.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Espírito Santo V, Passos J, Nzwalo H, Carvalho I, Santos F, Martins C, et al. Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience. J Neuro-Oncol. 2020;147:1–5. https://doi.org/10.1007/s11060-020-03443-6.

    Article  CAS  Google Scholar 

  40. French JA, Lawson JA, Yapici Z, et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet (London, England). 2016;388(10056):2153–63. https://doi.org/10.1016/S0140-6736(16)31419-2.

    Article  CAS  Google Scholar 

  41. Hua C, Zehou O, Ducassou S, Minard-Colin V, Hamel-Teillac D, Wolkenstein P, et al. Sirolimus improves pain in NF1 patients with severe plexiform neurofibromas. Pediatrics. 2014;133(6):e1792–7. https://doi.org/10.1542/peds.2013-1224.

    Article  PubMed  Google Scholar 

  42. Zehou O, Ferkal S, Brugieres P, Barbarot S, Bastuji-Garin S, Combemale P, et al. Absence of efficacy of everolimus in neurofibromatosis 1-related plexiform neurofibromas: results from a phase 2a trial. J Invest Dermatol. 2019;139(3):718–20. https://doi.org/10.1016/j.jid.2018.09.016.

    Article  CAS  PubMed  Google Scholar 

  43. Segal L, Darvish-Zargar M, Dilenge ME, Ortenberg J, Polomeno RC. Optic pathway gliomas in patients with neurofibromatosis type 1: follow-up of 44 patients. J AAPOS. 2010;14(2):155–8.

    Article  PubMed  Google Scholar 

  44. Mahdi J, Shah AC, Sato A, Morris SM, McKinstry RC, Listernick R, et al. A multi-institutional study of brainstem gliomas in children with neurofibromatosis type 1. Neurology. 2017;88(16):1584–9. https://doi.org/10.1212/WNL.0000000000003881.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Kornreich L, Blaser S, Schwarz M, Shuper A, Vishne TH, Cohen IJ, et al. Optic pathway glioma: correlation of imaging findings with the presence of neurofibromatosis. Am J Neuroradiol. 2001;22(10):1963–9.

    CAS  PubMed  Google Scholar 

  46. Doganis D, Pourtsidis A, Tsakiris K, Baka M, Kouri A, Bouhoutsou D, et al. Optic pathway glioma in children: 10 years of experience in a single institution. Pediatr Hematol Oncol. 2016;33(2):102–8. https://doi.org/10.3109/08880018.2016.1155101.

    Article  PubMed  Google Scholar 

  47. Ullrich NJ, Robertson R, Kinnamon DD, Scott RM, Kieran MW, Turner CD, et al. Moyamoya following cranial irradiation for primary brain tumors in children. Neurology. 2007;68(12):932–8. https://doi.org/10.1212/01.wnl.0000257095.33125.48.

    Article  CAS  PubMed  Google Scholar 

  48. Ater JL, Xia C, Mazewski CM, Booth TN, Freyer DR, Packer RJ, et al. Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: a report from the Children’s Oncology Group. Cancer. 2016;122(12):1928–36. https://doi.org/10.1002/cncr.29987.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dodgshun AJ, Elder JE, Hansford JR, Sullivan MJ. Long-term visual outcome after chemotherapy for optic pathway glioma in children: site and age are strongly predictive. Cancer. 2015;121(23):4190–6. https://doi.org/10.1002/cncr.29649.

    Article  PubMed  Google Scholar 

  50. Packer RJ, Lange B, Ater J, Nicholson HS, Allen J, Walker R, et al. Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol. 1993;11(5):850–6. https://doi.org/10.1200/JCO.1993.11.5.850.

    Article  CAS  PubMed  Google Scholar 

  51. Gururangan S, Cavazos CM, Ashley D, Herndon JE II, 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. https://doi.org/10.1200/JCO.2002.12.008.

    Article  CAS  PubMed  Google Scholar 

  52. Lassaletta A, Scheinemann K, Zelcer SM, Hukin J, Wilson BA, Jabado N, et al. Phase II weekly vinblastine for chemotherapy-naïve children with progressive low-grade glioma: a Canadian pediatric brain tumor consortium study. J Clin Oncol. 2016;34(29):3537–43. https://doi.org/10.1200/JCO.2016.68.1585.

    Article  CAS  PubMed  Google Scholar 

  53. Cappellano AM, Petrilli AS, da Silva NS, Silva FA, Paiva PM, Cavalheiro S, et al. Single agent vinorelbine in pediatric patients with progressive optic pathway glioma. J Neuro-Oncol. 2015;121(2):405–12. https://doi.org/10.1007/s11060-014-1652-6.

    Article  CAS  Google Scholar 

  54. Belsky J, Graham R, Leonard J, et al. LGG-33. MEK-Inhibitor monotherapy to treat concurrent optic glioma and metastatic neuroblastoma in a patient with neurofibromatosis type 1 (NF1). Neuro-Oncology. 2018;20(suppl_2):i111. https://doi.org/10.1093/neuonc/noy059.374.

    Article  PubMed Central  Google Scholar 

  55. •• Perreault S, Larouche V, Tabori U, et al. A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway: TRAM-01. BMC Cancer. 2019;19(1):1250. https://doi.org/10.1186/s12885-019-6442-2 This study describes the study design for a phase II study evaluating the activity of trametinib (MEK inhibitor) for treating optic pathway and other low-grade gliomas in pediatric patients including children with NF1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Karajannis MA, Legault G, Fisher MJ, Milla SS, Cohen KJ, Wisoff JH, et al. Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas. Neuro-Oncology. 2014;16(10):1408–16. https://doi.org/10.1093/neuonc/nou059.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Guillamo JS, Créange A, Kalifa C, et al. Prognostic factors of CNS tumours in Neurofibromatosis 1 (NF1): a retrospective study of 104 patients. Brain. 2003;126(1):152–60.

    Article  PubMed  Google Scholar 

  58. Strowd RE, Rodriguez FJ, Mclendon RE, et al. Histologically benign, clinically aggressive: Progressive non-optic pathway pilocytic astrocytomas in adults with NF1. Am J Med Genet Part A. 2016;170(6):1455–61. https://doi.org/10.1002/ajmg.a.37622.

    Article  CAS  PubMed  Google Scholar 

  59. Rodriguez FJ, Perry A, Gutmann DH, O'Neill BP, Leonard J, Bryant S, et al. Gliomas in neurofibromatosis type 1: a clinicopathologic study of 100 patients. J Neuropathol Exp Neurol. 2008;67(3):240–9.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Blakeley JO, Ye X, Duda DG, Halpin CF, Bergner AL, Muzikansky A, et al. Efficacy and biomarker study of bevacizumab for hearing loss resulting from neurofibromatosis type 2-associated vestibular schwannomas. J Clin Oncol. 2016;34(14):1669–75. https://doi.org/10.1200/JCO.2015.64.3817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. •• Plotkin SR, Duda DG, Muzikansky A, et al. Multicenter, prospective, phase II and biomarker study of high-dose bevacizumab as induction therapy in patients with neurofibromatosis type 2 and progressive vestibular schwannoma. J Clin Oncol. 2019;37(35):3446–54. https://doi.org/10.1200/JCO.19.01367 This study describes the results of a multicenter phase II study evaluating high-dose bevacizumab for NF2 patients with symptomatic vestibular schwannomas showing that high-dose bevacizumab led to favorable radiographic and hearing responses that were similar to prior lower dose regimens and indicating that responses were not as robust in children compared with adults.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Plotkin SR, Stemmer-Rachamimov AO, Barker FG, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361(4):358–67. https://doi.org/10.1056/NEJMoa0902579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Plotkin SR, Merker VL, Halpin C, Jennings D, McKenna MJ, Harris GJ, et al. Bevacizumab for progressive vestibular Schwannoma in neurofibromatosis type 2. Otol Neurotol. 2012;33(6):1046–52. https://doi.org/10.1097/MAO.0b013e31825e73f5.

    Article  PubMed  Google Scholar 

  64. Hochart A, Gaillard V, Baroncini M, André N, Vannier JP, Vinchon M, et al. Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2. J Neuro-Oncol. 2015;124:229–36. https://doi.org/10.1007/s11060-015-1828-8.

    Article  CAS  Google Scholar 

  65. Goutagny S, Kalamarides M. Medical treatment in neurofibromatosis type 2. Review of the literature and presentation of clinical reports. Neurochirurgie. 2018;64(5):370–4. https://doi.org/10.1016/j.neuchi.2016.09.004.

    Article  CAS  PubMed  Google Scholar 

  66. Alanin MC, Klausen C, Caye-Thomasen P, Thomsen C, Fugleholm K, Poulsgaard L, et al. Effect of bevacizumab on intracranial meningiomas in patients with neurofibromatosis type 2 – a retrospective case series. Int J Neurosci. 2016;126(11):1002–6. https://doi.org/10.3109/00207454.2015.1092443.

    Article  CAS  PubMed  Google Scholar 

  67. Morris KA, Golding JF, Axon PR, Afridi S, Blesing C, Ferner RE, et al. Bevacizumab in neurofibromatosis type 2 (NF2) related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation. Neurol Pract. 2016;3(4):281–9. https://doi.org/10.1093/nop/npv065.

    Article  Google Scholar 

  68. Sverak P, Adams ME, Haines SJ, Levine SC, Nascene D, Sommer K, et al. Bevacizumab for hearing preservation in neurofibromatosis type 2: emphasis on patient-reported outcomes and toxicities. Otolaryngol - Head Neck Surg (United States). 2019;160(3):526–32. https://doi.org/10.1177/0194599818809085.

    Article  Google Scholar 

  69. Karajannis MA, Legault G, Hagiwara M, Giancotti FG, Filatov A, Derman A, et al. Phase II study of everolimus in children and adults with neurofibromatosis type 2 and progressive vestibular schwannomas. Neuro-Oncology. 2014;16(2):292–7. https://doi.org/10.1093/neuonc/not150.

    Article  CAS  PubMed  Google Scholar 

  70. Goutagny S, Raymond E, Esposito-Farese M, Trunet S, Mawrin C, Bernardeschi D, et al. Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas. J Neuro-Oncol. 2015;122:313–20. https://doi.org/10.1007/s11060-014-1710-0.

    Article  CAS  Google Scholar 

  71. Plotkin SR, Halpin C, McKenna MJ, Loeffler JS, Batchelor TT, Barker FG. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol. 2010;31(7):1135–43. https://doi.org/10.1097/MAO.0b013e3181eb328a.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Antinheimo J, Sankila R, Carpén O, Pukkala E, Sainio M, Jääskeläinen J. Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas. Neurology. 2000;54(1):71–6.

    Article  CAS  PubMed  Google Scholar 

  73. Campian J, Gutmann DH. CNS tumors in Neurofibromatosis. J Clin Oncol. 2017;35:2378–85. https://doi.org/10.1200/JCO.2016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. •• Blakeley JO, Evans DG, Adler J, et al. Consensus recommendations for current treatments and accelerating clinical trials for patients with neurofibromatosis type 2. Am J Med Genet Part A. 2012;158 A(1):24–41. https://doi.org/10.1002/ajmg.a.34359 This is an excellent review of consensus recommendations for managing patient with NF2.

    Article  Google Scholar 

  75. Massick DD, Welling DB, Dodson EE, Scholfield M, Nagaraja HN, Schmalbrock P, et al. Tumor growth and audiometric change in vestibular schwannomas managed conservatively. Laryngoscope. 2000;110(11):1843–9. https://doi.org/10.1097/00005537-200011000-00015.

    Article  CAS  PubMed  Google Scholar 

  76. Ruggieri M, Praticò AD, Serra A, et al. Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Acta Otorhinolaryngol Ital. 2016;36(5):345–67. https://doi.org/10.14639/0392-100X-1093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Shukla A, Ba F-C, Hsu B, et al. Association between patient-reported outcomes and objective disease indices in people with NF2. Neurology Clinical Practice. 2019;9:322–9. https://doi.org/10.1212/CPJ.0000000000000648.

    Article  PubMed  PubMed Central  Google Scholar 

  78. 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  CAS  PubMed  Google Scholar 

  79. Chopra R, Kondziolka D, Niranjan A, Lunsford LD, Flickinger JC. Long-term follow-up of acoustic schwannoma radiosurgery with marginal tumor doses of 12 to 13 Gy. Int J Radiat Oncol Biol Phys. 2007;68(3):845–51. https://doi.org/10.1016/j.ijrobp.2007.01.001.

    Article  PubMed  Google Scholar 

  80. Chung LK, Nguyen TP, Sheppard JP, Lagman C, Tenn S, Lee P, et al. A systematic review of radiosurgery versus surgery for neurofibromatosis type 2 vestibular schwannomas. World Neurosurg. 2018;109:47–58. https://doi.org/10.1016/j.wneu.2017.08.159.

    Article  PubMed  Google Scholar 

  81. Morris KA, Golding JF, Blesing C, et al. Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort. J Neuro-Oncol. 2017;131(1):117–24. https://doi.org/10.1007/s11060-016-2276-9.

    Article  CAS  Google Scholar 

  82. Lu VM, Ravindran K, Graffeo CS, Perry A, van Gompel JJ, Daniels DJ, et al. Efficacy and safety of bevacizumab for vestibular schwannoma in neurofibromatosis type 2: a systematic review and meta-analysis of treatment outcomes. J Neuro-Oncol. 2019;144(2):239–48. https://doi.org/10.1007/s11060-019-03234-8.

    Article  CAS  Google Scholar 

  83. Slusarz KM, Merker VL, Muzikansky A, Francis SA, Plotkin SR. Long-term toxicity of bevacizumab therapy in neurofibromatosis 2 patients. Cancer Chemother Pharmacol. 2014;3:1197–204. https://doi.org/10.1007/s00280-014-2456-2.

    Article  CAS  Google Scholar 

  84. Birckhead B, Sio TT, Pollock BE, Link MJ, Laack NN. Gamma knife radiosurgery for neurofibromatosis type 2-associated meningiomas: a 22-year patient series. J Neuro-Oncol. 2016;130(3):553–60. https://doi.org/10.1007/s11060-016-2257-z.

    Article  CAS  Google Scholar 

  85. Plotkin SR, O’Donnell CC, Curry WT, Bove CM, MacCollin M, Nunes FP. Spinal ependymomas in neurofibromatosis type 2: a retrospective analysis of 55 patients: clinical article. J Neurosurg Spine. 2011;14(4):543–7. https://doi.org/10.3171/2010.11.SPINE10350.

    Article  PubMed  Google Scholar 

  86. Kalamarides M, Essayed W, Lejeune JP, Aboukais R, Sterkers O, Bernardeschi D, et al. Spinal ependymomas in NF2: a surgical disease? J Neuro-Oncol. 2018;136(3):605–11. https://doi.org/10.1007/s11060-017-2690-7.

    Article  CAS  Google Scholar 

  87. Blakeley J, Schreck KC, Evans DG, Korf BR, Zagzag D, Karajannis MA, et al. Clinical response to Bevacizumab in schwannomatosis. Neurology. 2014;83(21):1986–7. https://doi.org/10.1212/WNL.0000000000000997.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Internal Medicine, Section on Hematology and Oncology, and the Translational Sciences Institute, Wake Forest School of Medicine, 1 Medical Center Boulevard, Winston Salem, NC, 27157, USA

    Roy E Strowd III MD, MEd, MS

  2. Multidisciplinary Neurofibromatosis Clinic, Wake Forest Baptist Comprehensive Cancer Center, Wake Forest School of Medicine, 1 Medical Center Boulevard, Winston Salem, NC, 27157, USA

    Roy E Strowd III MD, MEd, MS

Authors
  1. Roy E Strowd III MD, MEd, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roy E Strowd III MD, MEd, MS.

Ethics declarations

Conflict of Interest

Roy E. Strowd serves as a consultant for Monteris Medical Inc., Novocure, and Nanobiotix; he receives an editorial stipend as Section Editor of the Resident and Fellow Section of Neurology(R) and has received research/grant support from the American Academy of Neurology, American Society of Clinical Oncology, Southeastern Brain Tumor Foundation, and Jazz Pharmaceuticals; however, none of these is relevant to this article.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Patients with Neurofibromatosis-Related Nervous System Tumors

This article is part of the Topical Collection on Neuro-oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Strowd, R.E. Available Therapies for Patients with Neurofibromatosis-Related Nervous System Tumors. Curr. Treat. Options in Oncol. 21, 81 (2020). https://doi.org/10.1007/s11864-020-00779-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-020-00779-z

Keywords

Search

Navigation