Skip to main content
SpringerLink
Log in

Clinical outcome of neurofibromatosis type 2-related vestibular schwannoma: treatment strategies and challenges

  • Original Article
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

To discuss the appropriate treatment strategy for NF2-related vestibular schwannoma (VS) according to our experiences, we analyzed long-term clinical and radiological data focusing on NF2-related VS patients. Seventeen NF2-related VS patients were included. Based on their first management modality for VS, we classified these patients into the following four groups: microsurgery (MS), fractionated gamma knife radiosurgery (f-GKS), single session gamma knife radiosurgery (s-GKS), and conservative management (CM). Each patient was assessed for each separate ear. Changes of tumor volume and hearing status for 32 ears in 17 patients according to their first treatment modality were evaluated. The mean follow-up duration and tumor volume of the MS (4 ears, 4 patients), f-GKS (12 ears, 10 patients), s-GKS (8 ears, 7 patients), and CM (8 ears, 7 patients) groups were 3.9 years and 1.6 mL; 5.1 years and 11.1 mL; 8.4 years and 5.6 mL; and 6.1 years and 1.6 mL, respectively. Relatively lower local control rates were observed in the MS and the CM group (0 and 12.5 %, respectively). On the other hand, better local control rates for follow-up periods of 5.1 and 8.4 years were achieved in the f-GKS and the s-GKS groups (75 and 50 %, respectively). However, hearing preservation in all treatment modalities could not be achieved effectively. Long-term preservation of hearing in at least one serviceable ear as well as tumor control should be considered for each patient. Therefore, a proper treatment option should be selected at the appropriate time according to clinical characteristics of individual patients.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Asthagiri AR, Parry DM, Butman JA, Kim HJ, Tsilou ET, Zhuang Z, Lonser RR (2009) Neurofibromatosis type 2. Lancet 373:1974–1986. doi:10.1016/s0140-6736(09)60259-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Brackmann DE, Fayad JN, Slattery WH 3rd, Friedman RA, Day JD, Hitselberger WE, Owens RM (2001) Early proactive management of vestibular schwannomas in neurofibromatosis type 2. Neurosurgery 49:274–280, discussion 280–283

    CAS  PubMed  Google Scholar 

  3. Briggs RJ, Brackmann DE, Baser ME, Hitselberger WE (1994) Comprehensive management of bilateral acoustic neuromas. Current perspectives. Arch Otolaryngol Head Neck Surg 120:1307–1314

    Article  CAS  PubMed  Google Scholar 

  4. Combs SE, Volk S, Schulz-Ertner D, Huber PE, Thilmann C, Debus J (2005) Management of acoustic neuromas with fractionated stereotactic radiotherapy (FSRT): long-term results in 106 patients treated in a single institution. Int J Radiat Oncol Biol Phys 63:75–81. doi:10.1016/j.ijrobp.2005.01.055

    Article  PubMed  Google Scholar 

  5. Dirks MS, Butman JA, Kim HJ, Wu T, Morgan K, Tran AP, Lonser RR, Asthagiri AR (2012) Long-term natural history of neurofibromatosis type 2-associated intracranial tumors. J Neurosurg 117:109–117. doi:10.3171/2012.3.jns111649

    Article  PubMed  PubMed Central  Google Scholar 

  6. Doyle KJ, Shelton C (1993) Hearing preservation in bilateral acoustic neuroma surgery. Am J Otol 14:562–565

    CAS  PubMed  Google Scholar 

  7. Evans DG (2009) Neurofibromatosis 2 [Bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]. Genet Med 11:599–610. doi:10.1097/GIM.0b013e3181ac9a27

    Article  PubMed  Google Scholar 

  8. Evans DG, Baser ME, O’Reilly B, Rowe J, Gleeson M, Saeed S, King A, Huson SM, Kerr R, Thomas N, Irving R, MacFarlane R, Ferner R, McLeod R, Moffat D, Ramsden R (2005) Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Br J Neurosurg 19:5–12. doi:10.1080/02688690500081206

    Article  CAS  PubMed  Google Scholar 

  9. Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V, Harris R (1992) A clinical study of type 2 neurofibromatosis. Q J Med 84:603–618

    CAS  PubMed  Google Scholar 

  10. Evans DG, Ramsden R, Huson SM, Harris R, Lye R, King TT (1993) Type 2 neurofibromatosis: the need for supraregional care? J Laryngol Otol 107:401–406

    Article  CAS  PubMed  Google Scholar 

  11. Ferri GG, Modugno GC, Calbucci F, Ceroni AR, Pirodda A (2009) Hearing loss in vestibular schwannomas: analysis of cochlear function by means of distortion-product otoacoustic emissions. Auris Nasus Larynx 36:644–648. doi:10.1016/j.anl.2009.02.006

    Article  PubMed  Google Scholar 

  12. Ferri GG, Modugno GC, Pirodda A, Fioravanti A, Calbucci F, Ceroni AR (2008) Conservative management of vestibular schwannomas: an effective strategy. Laryngoscope 118:951–957. doi:10.1097/MLG.0b013e31816a8955

    Article  PubMed  Google Scholar 

  13. Gardner G, Robertson JH (1988) Hearing preservation in unilateral acoustic neuroma surgery. Ann Otol Rhinol Laryngol 97:55–66

    Article  CAS  PubMed  Google Scholar 

  14. Hasegawa T, Kida Y, Kato T, Iizuka H, Yamamoto T (2011) Factors associated with hearing preservation after gamma knife surgery for vestibular schwannomas in patients who retain serviceable hearing. J Neurosurg 115:1078–1086. doi:10.3171/2011.7.jns11749

    Article  PubMed  Google Scholar 

  15. Ito E, Saito K, Yatsuya H, Nagatani T, Otsuka G (2009) Factors predicting growth of vestibular schwannoma in neurofibromatosis type 2. Neurosurg Rev 32:425–433. doi:10.1007/s10143-009-0223-3

    Article  PubMed  Google Scholar 

  16. Kida Y, Kobayashi T, Tanaka T, Mori Y (2000) Radiosurgery for bilateral neurinomas associated with neurofibromatosis type 2. Surg Neurol 53:383–389, discussion 389–390

    Article  CAS  PubMed  Google Scholar 

  17. Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC (1998) Long-term outcomes after radiosurgery for acoustic neuromas. N Engl J Med 339:1426–1433. doi:10.1056/nejm199811123392003

    Article  CAS  PubMed  Google Scholar 

  18. Lederman G, Arbit E, Odaimi M, Wertheim S, Lombardi E (1997) Recurrent glioblastoma multiforme: potential benefits using fractionated stereotactic radiotherapy and concurrent taxol. Stereotact Funct Neurosurg 69:162–174

    Article  CAS  PubMed  Google Scholar 

  19. MacNally SP, Rutherford SA, King AT, Freeman S, Thorne J, Mawman D, O’Driscoll MP, Evans DG, Ramsden RT (2009) Outcome from surgery for vestibular schwannomas in children. Br J Neurosurg 23:226–231. doi:10.1080/02688690902968844

    Article  PubMed  Google Scholar 

  20. Maier W, Grauvogel TD, Laszig R, Ridder GJ (2011) Value of different strategies in the treatment of vestibular schwannoma: therapeutic aspects and literature analysis. HNO 59:425–436. doi:10.1007/s00106-011-2302-3

    Article  CAS  PubMed  Google Scholar 

  21. Masuda A, Fisher LM, Oppenheimer ML, Iqbal Z, Slattery WH (2004) Hearing changes after diagnosis in neurofibromatosis type 2. Otol Neurotol 25:150–154

    Article  PubMed  Google Scholar 

  22. Mathieu D, Kondziolka D, Flickinger JC, Niranjan A, Williamson R, Martin JJ, Lunsford LD (2007) Stereotactic radiosurgery for vestibular schwannomas in patients with neurofibromatosis type 2: an analysis of tumor control, complications, and hearing preservation rates. Neurosurgery 60:460–468. doi:10.1227/01.neu.0000255340.26027.53, discussion 468–470

    PubMed  Google Scholar 

  23. Moffat DA, Quaranta N, Baguley DM, Hardy DG, Chang P (2003) Management strategies in neurofibromatosis type 2. Eur Arch Otorhinolaryngol 260:12–18. doi:10.1007/s00405-002-0503-9

    PubMed  Google Scholar 

  24. Odat HA, Piccirillo E, Sequino G, Taibah A, Sanna M (2011) Management strategy of vestibular schwannoma in neurofibromatosis type 2. Otol Neurotol 32:1163–1170. doi:10.1097/MAO.0b013e3182267f17

    Article  PubMed  Google Scholar 

  25. Piccirillo E, Guida M, Flanagan S, Lauda L, Fois P, Sanna M (2008) CNAP to predict functional cochlear nerve preservation in NF-2: cochlear implant or auditory brainstem implant. Skull Base 18:281–287. doi:10.1055/s-2008-1043753

    Article  PubMed  PubMed Central  Google Scholar 

  26. Poen JC, Golby AJ, Forster KM, Martin DP, Chinn DM, Hancock SL, Adler JR Jr (1999) Fractionated stereotactic radiosurgery and preservation of hearing in patients with vestibular schwannoma: a preliminary report. Neurosurgery 45:1299–1305, discussion 1305–1307

    Article  CAS  PubMed  Google Scholar 

  27. Roche PH, Regis J, Pellet W, Thomassin JM, Gregoire R, Dufour H, Peragut JC (2000) Neurofibromatosis type 2. Preliminary results of gamma knife radiosurgery of vestibular schwannomas. Neurochirurgie 46:339–353, discussion 354

    CAS  PubMed  Google Scholar 

  28. Rowe J, Radatz M, Kemeny A (2008) Radiosurgery for type II neurofibromatosis. Prog Neurol Surg 21:176–182. doi:10.1159/000156907

    Article  PubMed  Google Scholar 

  29. Rowe JG, Radatz MW, Walton L, Soanes T, Rodgers J, Kemeny AA (2003) Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofibromatosis. J Neurol Neurosurg Psychiatry 74:1288–1293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Samii M, Gerganov V, Samii A (2008) Microsurgery management of vestibular schwannomas in neurofibromatosis type 2: indications and results. Prog Neurol Surg 21:169–175. doi:10.1159/000156905

    Article  CAS  PubMed  Google Scholar 

  31. Samii M, Matthies C, Tatagiba M (1997) Management of vestibular schwannomas (acoustic neuromas): auditory and facial nerve function after resection of 120 vestibular schwannomas in patients with neurofibromatosis 2. Neurosurgery 40:696–705, discussion 705–706

    Article  CAS  PubMed  Google Scholar 

  32. Sanna M, Mancini F, Russo A, Taibah A, Falcioni M, Di Trapani G (2011) Atlas of acoustic neurinoma microsurgery, 2nd edn. Thieme, New York

    Google Scholar 

  33. Sharma MS, Singh R, Kale SS, Agrawal D, Sharma BS, Mahapatra AK (2010) Tumor control and hearing preservation after gamma knife radiosurgery for vestibular schwannomas in neurofibromatosis type 2. J Neurooncol 98:265–270. doi:10.1007/s11060-010-0181-1

    Article  PubMed  Google Scholar 

  34. Slattery WH 3rd, Brackmann DE, Hitselberger W (1998) Hearing preservation in neurofibromatosis type 2. Am J Otol 19:638–643

    PubMed  Google Scholar 

  35. Slattery WH 3rd, Fisher LM, Hitselberger W, Friedman RA, Brackmann DE (2007) Hearing preservation surgery for neurofibromatosis Type 2-related vestibular schwannoma in pediatric patients. J Neurosurg 106:255–260. doi:10.3171/ped.2007.106.4.255

    Article  PubMed  Google Scholar 

  36. Sughrue ME, Kane AJ, Kaur R, Barry JJ, Rutkowski MJ, Pitts LH, Cheung SW, Parsa AT (2011) A prospective study of hearing preservation in untreated vestibular schwannomas. J Neurosurg 114:381–385. doi:10.3171/2010.4.jns091962

    Article  PubMed  Google Scholar 

  37. Tysome JR, Macfarlane R, Durie-Gair J, Donnelly N, Mannion R, Knight R, Harris F, Vanat ZH, Tam YC, Burton K, Hensiek A, Raymond FL, Moffat DA, Axon PR (2012) Surgical management of vestibular schwannomas and hearing rehabilitation in neurofibromatosis type 2. Otol Neurotol 33:466–472. doi:10.1097/MAO.0b013e318248eaaa

    Article  PubMed  Google Scholar 

  38. Varlotto JM, Shrieve DC, Alexander E 3rd, Kooy HM, Black PM, Loeffler JS (1996) Fractionated stereotactic radiotherapy for the treatment of acoustic neuromas: preliminary results. Int J Radiat Oncol Biol Phys 36:141–145

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was equally supported by the Global Frontier Project grant (NRF-2012M3A6A-2010-0029781) of National Research Foundation funded by the Ministry of Education, Science and Technology of Korea and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (HI14C3418).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, 49267, South Korea

    Byung Sup Kim

  2. Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Ho Jun Seol, Jung-Il Lee, Hyung Jin Shin, Kwan Park, Doo-Sik Kong & Do-Hyun Nam

  3. Department of Otolaryngology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Yang-Sun Cho

Authors
  1. Byung Sup Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ho Jun Seol
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jung-Il Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hyung Jin Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kwan Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Doo-Sik Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Do-Hyun Nam
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yang-Sun Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ho Jun Seol or Yang-Sun Cho.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Funding

None.

Additional information

Comments

Mehmet Zileli, Izmir, Turkey

Management of neurofibromatosis type 2-related vestibular schwannomas is very controversial. Other than surgical removal, gamma knife surgery with single dose or fractionated forms, conservative follow up, and cochlear implants are the options in their treatment. This paper discusses all these management options in a series of 17 patients (32 ears) with long follow-up durations.

The authors have grouped patients: microsurgery group, fractionated gamma knife radiosurgery group, single-session gamma knife radiosurgery group and conservative management group.

Hearing preservation is the main concern in bilateral vestibular schwannomas. The authors have found lower local control rates in surgical group and conservatively followed group (0 and 12.5 %). None of the groups had significantly better hearing preservation. The algorhythm recommended by the authors is a very straightforward management protocol, and it presents the current knowledge which may be applied in most of the instances.

However, there are changing concepts and this algorhythm needs to be modified in the near future:

a) Microsurgery or gamma knife surgery for large volume tumors: If the tumor volume is quite small (1.6 ml in this series), conservative management—observation only—or microsurgical removal have been the procedure of choice. Gamma knife radiosurgery of vestibular schwannomas in patients with NF2 responded less well than did unilateral sporadic vestibular schwannomas (15). General tendency for tumors greater than 3 cm in diameter has been the surgical removal. However, there are some reports recommending gamma knife for them (2, 3, 7). Casentini et al. have used multisession stereotactic radiosurgery for large vestibular schwannomas (3).

A large cohort study from Netherland examining the outcomes after gamma knife surgery (9) has revealed that the tumor control rate has decreased from 94.1 % for tumors smaller than 0.5 cm3 to 80.7 % for tumors larger than 6 cm3. Whether gamma knife should be applied in single dose or fractionated is still not very clear.

b) Surgery and hearing preservation: Nowak et al. (13) has found that a significant deterioration to the non-functional level occurred in 19 out of 22 cases after surgery. They recommend early (in small volumes) surgical intervention to maintain hearing function. However, those small volume tumors are also good candidates for observation or gamma knife surgery.

c) Chemotherapy: Another concern is using chemotherapy during follow up period or in addition to microsurgery or gamma knife surgery (1, 4, 5, 6, 11, 14). Especially antiangiogenic drug Bevacizumab has been found to decrease the vestibular schwannomas growth rate (4, 6, 11). There are also efforts to use other anticancer drugs (5, 14).

d) Conservative management: Serial observation of vestibular schwannomas is a viable treatment strategy for selected patients (8). In tumors with NF2, serviceable hearing can be maintained for a significant length of time, making conservative management an attractive option (10). Kontorinis et al. have reported that the average annual vestibular schwannoma growth is 0.4 mm without any correlation with hearing loss. (10).

e) Genetic investigations: There is one report describing a genetic hallmark to differentiate large NF2-associated tumors from smaller tumors (12). We can predict some genetic test will be applicable to choose appropriate patients to wait or make interventions.

I thank the authors for reporting their experience with very long follow ups and presenting an algorhythm for those very challenging tumor groups. In the future, I predict we will have better outcomes and more hearing preservations without the need of cochlear implants in bilateral schwannomas in NF2 patients.

References

1-Bernardeschi D, Peyre M, Collin M, Smail M, Sterkers O, Kalamarides M. Internal Auditory Canal Decompression for Hearing Maintenance in Neurofibromatosis Type 2 Patients. Neurosurgery. 2015 Nov 16. [Epub ahead of print]

2-Boari N, Bailo M, Gagliardi F, Franzin A, Gemma M, del Vecchio A, Bolognesi A, Picozzi P, Mortini P. Gamma Knife radiosurgery for vestibular schwannoma: clinical results at long-term follow-up in a series of 379 patients. J Neurosurg. 2014 Dec;121 Suppl:123–42.

3-Casentini L, Fornezza U, Perini Z, Perissinotto E, Colombo F. Multisession stereotactic radiosurgery for large vestibular schwannomas. J Neurosurg. 2015 Apr;122(4):818–24. Epub 2015 Jan 16.

4-Farschtschi S, Kollmann P, Dalchow C, Stein A, Mautner VF. Reduced dosage of bevacizumab in treatment of vestibular schwannomas in patients with neurofibromatosis type 2. Eur Arch Otorhinolaryngol. 2015 Dec;272(12):3857–60

5-Goutagny S, Raymond E, Esposito-Farese M, Trunet S, Mawrin C, Bernardeschi D, Larroque B, Sterkers O, Giovannini M, Kalamarides M. Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas. J Neurooncol. 2015 Apr;122(2):313–20. Epub 2015 Jan 8.

6-Hochart A, Gaillard V, Baroncini M, André N, Vannier JP, Vinchon M, Dubrulle F, Lejeune JP, Vincent C, Nève V, Sudour Bonnange H, Bonne NX, Leblond P. Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosistype 2. J Neurooncol. 2015 Sep;124(2):229–36. Epub 2015 May 29.

7-Iorio-Morin C, AlSubaie F, Mathieu D. Safety and Efficacy of Gamma Knife Radiosurgery for the Management of Koos Grade 4 VestibularSchwannomas. Neurosurgery. 2016 Apr;78(4):521–30.

8-Jethanamest D, Rivera AM, Ji H, Chokkalingam V, Telischi FF, Angeli SI. Conservative management of vestibular schwannoma: Predictors of growth and hearing. Laryngoscope. 2015 Sep;125(9):2163–8. Epub 2015 Feb 3.

9-Klijn S, Verheul JB, Beute GN, Leenstra S, Mulder JJ, Kunst HP, Hanssens PE. Gamma Knife radiosurgery for vestibular schwannomas: evaluation of tumor control and its predictors in a large patient cohort in The Netherlands. J Neurosurg. 2015 Oct 2:1–8. [Epub ahead of print]

10-Kontorinis G, Nichani J, Freeman SR, Rutherford SA, Mills S, King AT, Mawman D, Huson S, O’Driscoll M, Gareth Evans D, Lloyd SK. Progress of hearing loss in neurofibromatosis type 2: implications for future management. Eur Arch Otorhinolaryngol. 2015 Nov;272(11):3143–50. Epub 2014 Oct 8.

11-Li KL, Djoukhadar I, Zhu X, Zhao S, Lloyd S, McCabe M, McBain C, Evans DG, Jackson A . Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response of vestibular schwannomato antiangiogenic therapy in type 2 neurofibromatosis. Neuro Oncol. 2016 Feb;18(2):275–82. Epub 2015 Aug 26.

12-Mehrian-Shai R, Freedman S, Shams S, Doherty J, Slattery W, Hsu NY, Reichardt JK, Andalibi A, Toren A. Schwannomas exhibit distinct size-dependent gene-expression patterns. Future Oncol. 2015;11(12):1751–8.

13-Nowak A, Dziedzic T, Czernicki T, Kunert P, Morawski K, Niemczyk K, Marchel A. Strategy for the surgical treatment of vestibular schwannomas in patients with neurofibromatosis type 2. Neurol Neurochir Pol. 2015;49(5):295–301. Epub 2015 Jul 3.

14-Plotkin SR, Singh MA, O’Donnell CC, Harris GJ, McClatchey AI, Halpin C. Audiologic and radiographic response of NF2-related vestibular schwannoma to erlotinib therapy. Nat Clin Pract Oncol. 2008 Aug;5(8):487–91. Epub 2008 Jun 17.

15-Sun S, Liu A. Long-term follow-up studies of Gamma Knife surgery for patients with neurofibromatosis Type 2. J Neurosurg. 2014 Dec;121 Suppl:143–9.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, B.S., Seol, H.J., Lee, JI. et al. Clinical outcome of neurofibromatosis type 2-related vestibular schwannoma: treatment strategies and challenges. Neurosurg Rev 39, 643–653 (2016). https://doi.org/10.1007/s10143-016-0728-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10143-016-0728-5

Keywords

Search

Navigation