Hearing and facial function outcomes for neurofibromatosis 2 clinical trials

Plotkin, Scott R.; Ardern‐Holmes, Simone; Barker, Fred G.; Blakeley, Jaishri O.; Evans, D. Gareth; Ferner, Robin E; Hadlock, Tessa A.; Halpin, Chris

doi:10.1212/01.wnl.0000435746.02780.f6

Cited by 37 publications

(43 citation statements)

References 35 publications

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“…An important limitation of the current observational retrospective cohort study arises from recall bias or inaccuracies in using historical data for determining age at loss of useful hearing in those patients in whom it occurred prior to 2010. Moreover, although more widely available, PTA is not as useful in assessing hearing in NF2 as ODS, and decibel rate of loss of hearing may not be helpful to patients. Furthermore, changes in treatment in recent years, such the introduction of bevacizumab, which may better preserve hearing compared with other modalities, may mean that historical data may not be accurate when applied to newly diagnosed patients being offered currently available treatment regimens.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with < 50% ODS, Bamford‐Kowal‐Bench sentence testing scores were also recorded to assess their candidacy for auditory implantation . ODS assessments were offered to all patients annually or more frequently since the start of the NF2 national service in 2010, with a few exceptions: patients who lost their serviceable hearing prior to 2010, as well patients who were nontestable due to either learning difficulties, insufficient English‐language understanding, or young age . In addition, pure‐tone average (PTA) was used as a secondary outcome measure given its widespread availability, especially for patients managed prior to 2010.…”

Section: Methodsmentioning

confidence: 99%

“…In patients with NF2 whose vestibular schwannomas are conservatively managed, hearing loss is usually gradual, although sudden sensorineural hearing loss has also been observed . Coupled to hearing loss, frequent concomitant poor vision further exacerbates communication issues and highlights the need for a multidisciplinary approach for optimal patient management …”

Section: Introductionmentioning

confidence: 99%

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Progression of hearing loss in neurofibromatosis type 2 according to genetic severity

et al. 2018

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Objectives/Hypothesis This study set out to describe the progression of hearing loss in patients with neurofibromatosis type 2 (NF2), treated in a quaternary multidisciplinary clinic. It also aimed to compare hearing loss across patients grouped according to a known genetic severity score to explore its utility for prognostication. Study Design Retrospective cohort study. Methods We conducted a study of 147 patients with confirmed NF2 diagnosis for a mean observational period of 10 years. Pure‐tone average (PTA), optimum discriminations scores (ODS), and genotype data were collected. Patients were classified according to hearing class (American Academy of Otolaryngology), their candidacy for auditory implantation (UK National NF2 consensus) and grouped by genetic severity as: 1 = tissue mosaic, 2A = mild classic, 2B = moderate classic, and 3 = severe. Survival analysis investigated the effect of genetic severity on the age of loss of serviceable hearing. Results Genetic severity was a significant predictor of hearing outcomes such as ODS, hearing classification, and maximum annual PTA deterioration. Although the overall median age of loss of serviceable hearing was 78 years, there was significant variation according to the genetic severity; the median for severe patients was 32 years compared to a median of 80 for tissue mosaic patients. Conclusions This is the first description of long‐term hearing outcomes in a clinical setting across a large heterogeneous cohort of patients with NF2. The results highlight the potential importance and benefit of considering the genetic severity score of patients when undertaking treatment decisions, as well as planning future natural history studies. Level of Evidence 2c Laryngoscope, 129:974–980, 2019

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Progression of hearing loss in neurofibromatosis type 2 according to genetic severity

et al. 2018

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“…A description of the REiNS International Collaboration and its 7 working groups and initial recommendations of 4 working groups were published previously in Neurology. [5][6][7][8][9][10] In brief, the imaging working group provided recommendations for the use of MRI with volumetric analysis to evaluate response in clinical trials targeting histologically benign nerve sheath tumors such as plexiform neurofibromas and vestibular schwannomas. 5 The patientreported outcomes (PRO) working group described their approach for the objective selection of PRO measures in NF trials, and they recommended the use of Numeric Rating Scale-11 (NRS-11) as a measure of pain intensity for manifestations associated with pain.…”

mentioning

confidence: 99%

“…6 Finally, the functional outcomes working group provided recommendations for hearing response measured by word recognition as primary endpoint in trials for NF2-related vestibular schwannomas. 7 Since the publication of these recommendations in 2013, a number of ongoing clinical trials have incorporated these outcome measures.…”

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confidence: 99%

Consensus for NF clinical trials

Widemann

Plotkin

2016

Neurology

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The neurofibromatoses (NFs) can result in substantial morbidity in affected patients. In order to accelerate the development of effective therapies for NF-related tumor and nontumor manifestations, the development of standardized meaningful outcome measures for clinical trials is critical. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established with the goal to develop consensus recommendations for outcome measures and endpoints in future NF trials and provided the first set of recommendations in a Neurology ® supplement in 2013. This second supplement updates on clinical trials that have incorporated the recommended measures and provides new recommendations for (1) standardized and specific cognitive assessment tools for use in NF clinical trials, (2) patient-reported outcome measures including pain and physical functioning, (3) functional outcome measures for airway plexiform neurofibromas, (4) the use of whole-body MRI in NF, and (5) the development of biomarkers in NF and guidelines for collection of biospecimens and establishment of biobanks for neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis. Through engagement of the NF research community, regulatory agencies, NF advocacy groups, industry, and patients with NF, REiNS will provide a framework for comprehensive review of these recommendations, continue development of outcome measures relevant to patients, and compare results of trials, which use identical outcome measures. Neurology ® 2016;87 (Suppl 1):S1-S3 GLOSSARY NF 5 neurofibromatosis; NF1 5 neurofibromatosis 1; NF2 5 neurofibromatosis 2; NRS-11 5 Numeric Rating Scale-11; PRO 5 patient-reported outcomes; REiNS 5 Response Evaluation in Neurofibromatosis and Schwannomatosis.The NFs-including NF1, NF2, and schwannomatosis-are genetic tumor-predisposition syndromes characterized by the development of multiple tumor manifestations, in particular nerve sheath tumors, for most of which no standard treatment options other than surgery exist. [1][2][3] In addition, patients with NF can develop multiple nontumor manifestations, affecting many organ systems, which can result in substantial morbidity and reduced quality of life. There is an unmet need for effective medical therapies for NF-related manifestations. Differences between NF-related tumors and nonsyndromic solid cancers have limited the applicability of clinical trial designs used in oncology trials to the development of trials for NF. 4 The REiNS International Collaboration was established in 2011 with the primary goal to achieve consensus within the NF community for outcome measures and endpoints for future NF trials. A description of the REiNS International Collaboration and its 7 working groups and initial recommendations of 4 working groups were published previously in Neurology. 5-10In brief, the imaging working group provided recommendations for the use of MRI with volumetric analysis to evaluate response in clinical trials targeting histologically beni...

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Stereotactic Radiosurgery and Radiotherapy for Vestibular Schwannoma in NF2‐Related Schwannomatosis

Shrivastava,

Emmanouil,

Mathew

et al. 2023

The Laryngoscope

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ObjectivesTo determine the long‐term control rates and hearing outcomes for growing vestibular schwannoma in NF2‐related schwannomatosis (NF2) treated with stereotactic radiosurgery (SRS) and fractionated radiotherapy (FRT).MethodsRetrospective review of all patients treated with SRS/FRT between 1986 and2021 from a tertiary NF2 unit. Overall tumor control was defined as: (1) growth control (growth failure was defined as growth in any dimension of 3 millimetres or more from baseline post‐SRS/FRT), and (2) treatment control (no need for further intervention). Loss of serviceable hearing was defined as a drop in speech discrimination score below 50% after SRS/FRT.ResultsThere were 81 cases, with a mean duration of follow‐up of 125 months. Overall control rate was 72% (58/81), with 80% (65/81) growth control and 74% (60/81) treatment control. There was a 5‐year actuarial survival of 77% and 10‐year survival of 71%. Forty‐three percent (30/69) of cases did not have serviceable hearing at baseline. Of those remaining, 49% (19/39) preserved serviceable hearing during follow‐up at a mean of 106 months. Actuarial survival for preservation of serviceable hearing at 5 and 10 years was 69% and 53%. There were poorer outcomes with increasing genetic severity, and with baseline tumor size >3 cm. No cases of SRS/FRT‐related malignancy were identified at a mean follow‐up of 10 years.ConclusionStereotactic radiosurgery/fractionated radiotherapy are an effective option to treat growing vestibular schwannoma in patients with NF2 with the potential for hearing preservation in a proportion of patients.Level of EvidenceLevel 4—Case Series Laryngoscope, 2023

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Hearing and facial function outcomes for neurofibromatosis 2 clinical trials

Cited by 37 publications

References 35 publications

Progression of hearing loss in neurofibromatosis type 2 according to genetic severity

Progression of hearing loss in neurofibromatosis type 2 according to genetic severity

Consensus for NF clinical trials

Stereotactic Radiosurgery and Radiotherapy for Vestibular Schwannoma in NF2‐Related Schwannomatosis

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