Katrina A Morris1, John F Golding1, Patrick R Axon1, Shazia Afridi1, Claire Blesing1, Rosalie E Ferner1, Dorothy Halliday1, Raj Jena1, Pieter M Pretorius1, D Gareth Evans1, Martin G McCabe1, Allyson Parry1. 1. Nuffield Department of Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK (K.A.M., A.P.); University of New South Wales, St Vincent's Clinical School, Darlinghurst, Australia (K.A.M.); University of Westminster, London, UK (J.F.G.); Institute of Psychiatry, King's College, London, UK (J.F.G., R.E.F.); Addenbrooke's Hospital, Cambridge, UK (P.R.A.); Department of Neurology, Guy's & St Thomas' Hospital, London, UK (S.A., R.E.F.); Oxford University Hospitals NHS Trust, Oxford, UK (D.H., C.B., A.P., P.M.P.); Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (R.J.); Genomic Medicine, Institute of Human Development, MAHSC, University of Manchester, St Mary's Hospital, Manchester, UK (D.G.E.); Centre for Paediatric, Teenage and Young Adult Cancer, Institute of Cancer Sciences, University of Manchester, Manchester, UK (M.G.M.).
Abstract
BACKGROUND: NF2 patients develop multiple nervous system tumors including bilateral vestibular schwannomas (VS). The tumors and their surgical treatment are associated with deafness, neurological disability, and mortality.Medical treatment with bevacizumab has been reported to reduce VS growth and to improve hearing. In addition to evaluating these effects, this study also aimed to determine other important consequences of treatment including patient-reported quality of life and the impact of treatment on surgical VS rates. METHODS: Patients treated with bevacizumab underwent serial prospective MRI, audiology, clinical, CTCAE-4.0 adverse events, and NFTI-QOL quality-of-life assessments. Tumor volumetrics were classified according to the REiNs criteria and annual VS surgical rates reviewed. RESULTS: Sixty-one patients (59% male), median age 25 years (range, 10-57), were reviewed. Median follow-up was 23 months (range, 3-53). Partial volumetric tumor response (all tumors) was seen in 39% and 51% had stabilization of previously growing tumors. Age and pretreatment growth rate were predictors of response. Hearing was maintained or improved in 86% of assessable patients. Mean NFTI-QOL scores improved from 12.0 to 10.7 (P < .05). Hypertension was observed in 30% and proteinuria in 16%. Twelve treatment breaks occurred due to adverse events. The rates of VS surgery decreased after the introduction of bevacizumab. CONCLUSION: Treatment with bevacizumab in this large, UK-wide cohort decreased VS growth rates and improved hearing and quality of life. The potential risk of surgical iatrogenic damage was also reduced due to an associated reduction in VS surgical rates. Ongoing follow-up of this cohort will determine the long-term benefits and risks of bevacizumab treatment.
BACKGROUND: NF2 patients develop multiple nervous system tumors including bilateral vestibular schwannomas (VS). The tumors and their surgical treatment are associated with deafness, neurological disability, and mortality.Medical treatment with bevacizumab has been reported to reduce VS growth and to improve hearing. In addition to evaluating these effects, this study also aimed to determine other important consequences of treatment including patient-reported quality of life and the impact of treatment on surgical VS rates. METHODS: Patients treated with bevacizumab underwent serial prospective MRI, audiology, clinical, CTCAE-4.0 adverse events, and NFTI-QOL quality-of-life assessments. Tumor volumetrics were classified according to the REiNs criteria and annual VS surgical rates reviewed. RESULTS: Sixty-one patients (59% male), median age 25 years (range, 10-57), were reviewed. Median follow-up was 23 months (range, 3-53). Partial volumetric tumor response (all tumors) was seen in 39% and 51% had stabilization of previously growing tumors. Age and pretreatment growth rate were predictors of response. Hearing was maintained or improved in 86% of assessable patients. Mean NFTI-QOL scores improved from 12.0 to 10.7 (P < .05). Hypertension was observed in 30% and proteinuria in 16%. Twelve treatment breaks occurred due to adverse events. The rates of VS surgery decreased after the introduction of bevacizumab. CONCLUSION: Treatment with bevacizumab in this large, UK-wide cohort decreased VS growth rates and improved hearing and quality of life. The potential risk of surgical iatrogenic damage was also reduced due to an associated reduction in VS surgical rates. Ongoing follow-up of this cohort will determine the long-term benefits and risks of bevacizumab treatment.
Entities:
Keywords:
bevacizumab; neurofibromatosis type 2; schwannoma; vestibular schwannoma
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