{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T05:34:57Z","timestamp":1772602497353,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Economic Affairs and Climate and the HollandPTC consortium\u2014Erasmus MC, Rotterdam"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>(1) Background: This study aimed to evaluate the efficacy and treatment-related toxicity of proton radiotherapy (PRT) for vestibular schwannoma (VS) in patients with neurofibromatosis type 2-related schwannomatosis (NF2). (2) Methods: Consecutive NF2 patients treated with PRT for VS between 2004 and 2016 were retrospectively evaluated, focusing on tumor volume, facial and trigeminal nerve function, hearing, tinnitus, vestibular symptoms, and the need for salvage therapy after PRT. (3) Results: Eight patients were included (median age 36 years, 50% female). Median follow-up was 71 months. Five (63%) patients received fractionated PRT and three (38%) received PRT radiosurgery for VS. Six patients (75%) received prior VS surgery; three also received bevacizumab. Six patients (75%) did not require salvage therapy after PRT. Two patients (25%) with residual hearing lost it after PRT, and six had already lost ipsilateral hearing prior to PRT. Tumor and treatment-related morbidity could be evaluated in six patients. Following PRT, conditions that occurred or worsened were: facial paresis in five (83%), trigeminal hypoesthesia in two (33%), tinnitus in two (33%), and vestibular symptoms in four patients (67%). (4) Conclusion: After PRT for VS, the majority of the NF2 patients in the cohort did not require additional therapy. Tumor and\/or treatment-related cranial nerve deficits were common. This is at least partly explained by the use of PRT as a salvage treatment after surgery or bevacizumab, in the majority of cases. There remains the further opportunity to elucidate the efficacy and toxicity of proton radiotherapy as a primary treatment.<\/jats:p>","DOI":"10.3390\/curroncol30030263","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T07:06:37Z","timestamp":1679295997000},"page":"3473-3483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proton Radiotherapy for Vestibular Schwannomas in Patients with NF2-Related Schwannomatosis: A Case Series"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8232-576X","authenticated-orcid":false,"given":"Jules P. J.","family":"Douwes","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberley S.","family":"Koetsier","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor S.","family":"van Dam","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Erasmus MC, 3015 GD Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott R.","family":"Plotkin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederick G.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9963-469X","authenticated-orcid":false,"given":"D. Bradley","family":"Welling","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3955-0152","authenticated-orcid":false,"given":"Jeroen C.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-7421","authenticated-orcid":false,"given":"Erik F.","family":"Hensen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen A.","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., Mirzaa, G.M., and Amemiya, A. (1993). GeneReviews(R), University of Washington."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1097\/MAO.0000000000000239","article-title":"Natural History of Vestibular Schwannoma Growth and Hearing Decline in Newly Diagnosed Neurofibromatosis Type 2 Patients","volume":"35","author":"Plotkin","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.gim.2022.05.007","article-title":"Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation","volume":"24","author":"Plotkin","year":"2022","journal-title":"Genet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/ajmg.a.34359","article-title":"Consensus recommendations for current treatments and accelerating clinical trials for patients with neurofibromatosis type 2","volume":"158A","author":"Blakeley","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1093\/neuonc\/nou317","article-title":"Evidence of polyclonality in neurofibromatosis type 2\u2013associated multilobulated vestibular schwannomas","volume":"17","author":"Dewan","year":"2015","journal-title":"Neuro. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1055\/s-0032-1301396","article-title":"The NFTI-QOL: A Disease-Specific Quality of Life Questionnaire for Neurofibromatosis 2","volume":"73","author":"Hornigold","year":"2012","journal-title":"J. Neurol. Surg. B Skull Base"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1055\/s-2005-837581","article-title":"Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: A study of 24 patients","volume":"36","author":"Ruggieri","year":"2005","journal-title":"Neuropediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1136\/jmedgenet-2017-104519","article-title":"Genetic Severity Score predicts clinical phenotype in NF2","volume":"54","author":"Halliday","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1097\/MAO.0000000000000272","article-title":"Neurofibromatosis Type 2 Vestibular Schwannoma Treatment: A Review of the Literature, Trends, and Outcomes","volume":"35","author":"Maniakas","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/14737175.2018.1399795","article-title":"An update on the diagnosis and treatment of vestibular schwannoma","volume":"18","author":"Halliday","year":"2018","journal-title":"Expert Rev. Neurother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/neuonc\/noz153","article-title":"EANO guideline on the diagnosis and treatment of vestibular schwannoma","volume":"22","author":"Goldbrunner","year":"2020","journal-title":"Neuro. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s00701-017-3164-6","article-title":"Stereotactic radiosurgery vs. fractionated radiotherapy for tumor control in vestibular schwannoma patients: A systematic review","volume":"159","author":"Persson","year":"2017","journal-title":"Acta Neurochir."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s11060-021-03910-8","article-title":"Stereotactic radiosurgery for vestibular schwannomas in neurofibromatosis type 2 patients: A systematic review and meta-analysis","volume":"156","author":"Tosi","year":"2022","journal-title":"J. Neurooncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/jnci\/84.3.155","article-title":"Proton Beams in Radiation Therapy","volume":"84","author":"Suit","year":"1992","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.oraloncology.2018.11.015","article-title":"Intensity modulated proton therapy (IMPT)\u2014The future of IMRT for head and neck cancer","volume":"88","author":"Moreno","year":"2019","journal-title":"Oral Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.radonc.2019.08.019","article-title":"Lower doses to hippocampi and other brain structures for skull-base meningiomas with intensity modulated proton therapy compared to photon therapy","volume":"142","author":"Florijn","year":"2020","journal-title":"Radiother. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ctrv.2018.11.004","article-title":"Proton therapy for treatment of intracranial benign tumors in adults: A systematic review","volume":"72","author":"Lesueur","year":"2019","journal-title":"Cancer Treat. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1097\/MAO.0000000000003313","article-title":"Outcome and Toxicity of Proton Therapy for Vestibular Schwannoma: A Cohort Study","volume":"42","author":"Koetsier","year":"2021","journal-title":"Otol. Neurotol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"772831","DOI":"10.3389\/fonc.2021.772831","article-title":"Effectiveness and Toxicity of Fractionated Proton Beam Radiotherapy for Cranial Nerve Schwannoma Unsuitable for Stereotactic Radiosurgery","volume":"11","author":"Eichkorn","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1136\/jmg.2005.036319","article-title":"Malignant transformation and new primary tumours after therapeutic radiation for benign disease: Substantial risks in certain tumour prone syndromes","volume":"43","author":"Evans","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/GIM.0b013e318211faa9","article-title":"Empirical development of improved diagnostic criteria for neurofibromatosis 2","volume":"13","author":"Baser","year":"2011","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.ijrobp.2010.10.010","article-title":"Radiotherapy for Vestibular Schwannomas: A Critical Review","volume":"79","author":"Murphy","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1212\/01.wnl.0000435744.57038.af","article-title":"Recommendations for imaging tumor response in neurofibromatosis clinical trials","volume":"81","author":"Dombi","year":"2013","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"(1995). Committee on Hearing and Equilibrium Guidelines for the Evaluation of Hearing Preservation in Acoustic Neuroma (Vestibular Schwannoma): Committee on Hearing and Equilibrium. Otolaryngol. Head Neck. Surg., 113, 179\u2013180.","DOI":"10.1016\/S0194-5998(95)70101-X"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1177\/000348948809700110","article-title":"Hearing Preservation in Unilateral Acoustic Neuroma Surgery","volume":"97","author":"Gardner","year":"1988","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1177\/019459988509300202","article-title":"Facial Nerve Grading System","volume":"93","author":"House","year":"1985","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s13566-019-00410-1","article-title":"Clinical outcomes and toxicity of proton radiotherapy for vestibular schwannomas: A systematic review","volume":"8","author":"Koetsier","year":"2019","journal-title":"J. Radiat. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"K\u00fcchler, M., El Shafie, R.A., Adeberg, S., Herfarth, K., K\u00f6nig, L., Lang, K., H\u00f6rner-Rieber, J., Plinkert, P.K., Wick, W., and Sahm, F. (2022). Outcome after Radiotherapy for Vestibular Schwannomas (VS)-Differences in Tumor Control, Symptoms and Quality of Life after Radiotherapy with Photon versus Proton Therapy. Cancers, 14.","DOI":"10.3390\/cancers14081916"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1136\/jnnp.74.9.1288","article-title":"Clinical experience with gamma knife stereotactic radiosurgery in the management of vestibular schwannomas secondary to type 2 neurofibromatosis","volume":"74","author":"Rowe","year":"2003","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3171\/2016.9.JNS161463","article-title":"Gamma Knife radiosurgery for treatment of growing vestibular schwannomas in patients with neurofibromatosis Type 2: A matched cohort study with sporadic vestibular schwannomas","volume":"128","author":"Kruyt","year":"2018","journal-title":"J. Neurosurg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.wneu.2017.08.159","article-title":"A Systematic Review of Radiosurgery Versus Surgery for Neurofibromatosis Type 2 Vestibular Schwannomas","volume":"109","author":"Chung","year":"2018","journal-title":"World Neurosurg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/02688690500081206","article-title":"Management of the patient and family with neurofibromatosis 2: A consensus conference statement","volume":"19","author":"Evans","year":"2005","journal-title":"Br. J. Neurosurg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1750-1172-4-16","article-title":"Neurofibromatosis type 2 (NF2): A clinical and molecular review","volume":"4","author":"Evans","year":"2009","journal-title":"Orphanet J. Rare Dis."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/30\/3\/263\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:58:57Z","timestamp":1760122737000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/30\/3\/263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,20]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["curroncol30030263"],"URL":"https:\/\/doi.org\/10.3390\/curroncol30030263","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,20]]}}}