scholarly journals Managing NF2-associated vestibular schwannomas in children and young adults: review of an institutional series regarding effects of surgery and bevacizumab on growth rates, tumor volume, and hearing quality

2020 ◽  
Vol 36 (10) ◽  
pp. 2471-2480
Author(s):  
Isabel Gugel ◽  
Julian Zipfel ◽  
Philip Hartjen ◽  
Lan Kluwe ◽  
Marcos Tatagiba ◽  
...  
Keyword(s):  
Growth Rate ◽  
Young Adults ◽  
Growth Rates ◽  
Tumor Volume ◽  
Tumor Resection ◽  
Internal Auditory Canal ◽  
Hearing Preservation ◽  
Data Sets ◽  
Bevacizumab Treatment ◽  
Children And Young Adults

Abstract We reviewed our experience in managing of NF2-associated vestibular schwannoma (VS) in children and young adults regarding the effect of surgery and postoperative bevacizumab treatment. A total of 579 volumetric and hearing data sets were analyzed. The effect of surgery on tumor volume and growth rate was investigated in 46 tumors and on hearing function in 39 tumors. Long-term hearing follow-up behavior was compared with 20 non-operated ears in additional 15 patients. Sixteen operated VS were treated with bevacizumab. Mutation analysis of the NF2 gene was performed in 25 patients. Surgery significantly slowed down VS growth rate. Factors associated with a higher growth rate were increasing patient age, tumor volume, and constitutional truncating mutations. Immediately after surgery, functional hearing was maintained in 82% of ears. Deterioration of hearing was associated with initial hearing quality, larger tumor volumes, and larger resection amounts. Average hearing scores were initially better in the group of non-operated VS. Over time, hearing scores in both groups worsened with a similar dynamic. During bevacizumab treatment of residual tumors, four different patterns of growth were observed. Decompression of the internal auditory canal with various degrees of tumor resection decreases the postoperative tumor growth rates. Carefully tailored BAEP-guided surgery does not cause additional hearing deterioration. Secondary bevacizumab treatment showed heterogenous effects both regarding tumor size and hearing preservation. It seems that postoperative tumor residuals, that grow slower, behave differently to bevacizumab than reported for not-operated faster growing VS.

Management of NF2-associated vestibular schwannomas in children and young adults: influence of surgery and clinical factors on tumor volume and growth rate

2019 ◽  
Vol 24 (5) ◽  
pp. 584-592 ◽  
Author(s):  
Isabel Gugel ◽  
Florian Grimm ◽  
Christian Teuber ◽  
Lan Kluwe ◽  
Victor-Felix Mautner ◽  
...  
Keyword(s):  
Growth Rate ◽  
Young Adults ◽  
Tumor Volume ◽  
Statistical Significance ◽  
Tumor Resection ◽  
Internal Auditory Canal ◽  
Vestibular Schwannomas ◽  
Clinical Factors ◽  
Before And After ◽  
Children And Young Adults

OBJECTIVEThe authors’ aim was to evaluate the tumor volume and growth rate of neurofibromatosis type 2 (NF2)–associated vestibular schwannomas (VSs) and the clinical factors or type of mutations before and after surgery in children and adults younger than 25 years at the time of diagnosis.METHODSA total of 579 volumetric measurements were performed in 46 operated tumors in 28 NF2 patients, using thin-slice (< 3 mm) T1-weighted contrast-enhanced MRI. The follow-up period ranged from 21 to 167 months (mean 75 months). Growth rate was calculated using a multilinear regression model. Mutation analysis of the NF2 gene was performed in 25 patients.RESULTSSurgery significantly (p = 0.013) slowed the VS growth rate from 0.69 ± 1.30 cm3/yr to 0.23 ± 0.42 cm3/yr. Factors significantly associated with a higher growth rate of VSs were increasing patient age (p < 0.0005), tumor volume (p = 0.006), tumor size (p = 0.001), and constitutional truncating mutations in the NF2 gene (p = 0.018). VS growth rates tended to be higher in patients with spinal ependymomas and in right-sided tumors and lower in the presence of peripheral schwannomas; however, no statistical significance was achieved.CONCLUSIONSDecompression of the internal auditory canal with various degrees of tumor resection decreases the postoperative tumor growth rate in children and young adults with NF2-associated VS. Patients with potential risk factors for accelerated growth (e.g., large volume, truncating mutations) and with increasing age should be monitored more closely before and after surgery.

Bevacizumab for Hearing Preservation in Neurofibromatosis Type 2: Emphasis on Patient-Reported Outcomes and Toxicities

2018 ◽  
Vol 160 (3) ◽  
pp. 526-532 ◽  
Author(s):  
Pavlina Sverak ◽  
Meredith E. Adams ◽  
Stephen J. Haines ◽  
Samuel C. Levine ◽  
David Nascene ◽  
...  
Keyword(s):  
Patient Reported Outcomes ◽  
Tumor Volume ◽  
Neurofibromatosis Type ◽  
Hearing Preservation ◽  
Neurofibromatosis Type 2 ◽  
Hearing Improvement ◽  
Radiographic Response ◽  
Bevacizumab Treatment ◽  
Patient Reported

Objective Bevacizumab for hearing preservation in patients with neurofibromatosis type 2 (NF2) is an emerging practice. We set out to characterize the effectiveness and toxicity of bevacizumab in our patient group. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods Seventeen consecutive patients with NF2 received bevacizumab treatment for vestibular schwannomas, including 2 patients treated to maintain cochlear implant performance. Volumetric analysis of serial magnetic resonance imaging scans was used to evaluate radiographic response, and hearing response was evaluated with serial audiograms. Patient-reported outcomes were also assessed, including subjective hearing improvement, changes in tinnitus, vertigo, headaches, ear pain, and improvement in ability to communicate via telephone. Results A positive radiographic response occurred in 8 of 17 (47%) patients and the median tumor volume change was a tumor decrease of 19%. A positive hearing response was recorded in 5 of 9 (56%) patients. Two patients had a word recognition score improvement over 40%. There was an approximately 40% improvement in patient-reported outcomes. Primary toxicities included hypertension, proteinuria, dysgeusia, and amenorrhea. Conclusion Bevacizumab treatment was followed by hearing improvement in 56% of patients, while decreased tumor volume was noted in 47%. These outcomes agree favorably with prior reported series. There were significant improvements in patient-reported outcomes that have not been described previously.

Hearing Preservation After Microsurgical Resection of Large Vestibular Schwannomas

Neurosurgery ◽  
2011 ◽  
Vol 68 (3) ◽  
pp. 632-640 ◽  
Author(s):  
Salvatore Di Maio ◽  
A Daniel Malebranche ◽  
Brian Westerberg ◽  
Ryojo Akagami
Keyword(s):  
Cerebrospinal Fluid ◽  
Tumor Volume ◽  
Internal Auditory Canal ◽  
Longitudinal Axis ◽  
Hearing Preservation ◽  
Complete Resection ◽  
Tumor Diameter ◽  
Microsurgical Resection ◽  
Preservation Rate

Abstract BACKGROUND: Hearing, which is often still clinically useful at presentation even with larger tumors, is a major determinant of quality of life in vestibular schwannoma (VS) patients. OBJECTIVE: To present the hearing preservation rate after surgery in patients with large (≥3 cm) VSs and identify clinical or radiologic predictors of hearing preservation. METHODS: From April 2003 to March 2009, 192 patients underwent resection of a VS, including 46 large (≥3 cm) tumors, of whom 28 had serviceable hearing preoperatively. Six of 28 patients (21.4%) had preserved hearing postoperatively. RESULTS: Mean tumor diameter was 3.6 cm (range, 3.0-5.0 cm) and tumor volume was 17.2 mL (range, 6.9-45.2 mL). For patients with grade A Sanna-Fukushima hearing, the hearing preservation rate was 4 of 11 (36.4%). Complete resection was achieved in 6 of 6 cases with hearing preservation (41/47 for all patients). Six of 6 patients with preserved hearing had a cerebrospinal fluid cleft in the internal auditory canal (IAC) compared with 9 of 16 patients without preoperative hearing and 9 of 20 for patients with serviceable hearing that was lost postoperatively (P = .045). Six of 6 patients with preserved hearing had less than 35% of the tumor anterior to the longitudinal axis of the IAC compared with 13 of 20 in the serviceable hearing that was lost group (P = .036). CONCLUSION: Our series demonstrates hearing preservation is possible for patients with large VSs and should be attempted in all patients with preoperative hearing. The quality of preoperative hearing, a cerebrospinal fluid cleft at the apex of the IAC, and a smaller proportion of tumor anterior to the IAC were positively associated with hearing preservation.

Left-sided retrosigmoid craniotomy for the resection of a vestibular schwannoma

2014 ◽  
Vol 36 (v1supplement) ◽  
pp. 1 ◽  
Author(s):  
Peter S. Amenta ◽  
Jacques J. Morcos
Keyword(s):  
Vestibular Schwannoma ◽  
Tumor Resection ◽  
Cranial Nerves ◽  
Internal Auditory Canal ◽  
Patient Positioning ◽  
Standard Technique ◽  
Hearing Preservation ◽  
Surgical Access ◽  
Wide Range ◽  
Primary Means

The cerebellopontine angle is the site for a wide-range of neoplastic and vascular pathologies. The retrosigmoid craniotomy remains the primary means by which to gain surgical access to this anatomically complex region. We present our standard technique for the completion of a retrosigmoid craniotomy and the resection of a left-sided vestibular schwannoma. Anatomy pertinent to the approach, including, the transverse and sigmoid sinuses, cranial nerves, and internal auditory canal (IAC) is displayed. Special emphasis is placed on patient positioning, adequate bone removal, and tumor resection. The drilling of the IAC and tumor dissection from the VII-VIII complex is also highlighted. Hearing preservation was achieved.The video can be found here: http://youtu.be/FFZju5vcBi0.

scholarly journals RTHP-28. TTFIELDS TREATMENT AFFECTS TUMOR GROWTH RATES: A POST-HOC ANALYSIS OF THE PIVOTAL PHASE 3 EF-14 TRIAL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi215-vi215
Author(s):  
Noa Urman ◽  
Gitit Lavy-Shahaf ◽  
Shay levi ◽  
Ze’ev Bomzon
Keyword(s):  
Growth Rate ◽  
Tumor Growth ◽  
Growth Rates ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Local Tumor Control ◽  
Tumor Growth Rate ◽  
Tumor Control ◽  
Pivotal Phase ◽  
Tumor Treating Fields

Abstract INTRODUCTION The pivotal EF-14 trial showed that Tumor Treating Fields (TTFields) extend Progression Free Survival (PFS) in newly Diagnosed Glioblastoma (ndGBM) patients. This leads to the hypothesis that TTFields therapy leads to local control of tumors, yielding a significant decrease in tumor growth rates. Here we present an analysis testing this hypothesis in biopsy-only patients who participated in the EF-14 trial. METHODS Biopsy patients of the EF-14 trial who exhibited radiological progression were included in this study (treatment: N=37/60, control: N=12/29). Volumes of enhancing tumor were segmented on T1c MRIs at baseline and at progression. Tumor growth rate was calculated as: growth_rate=(ln(v0)-ln(v1))/dt. (v0- tumor volume at baseline), v1- Tumor volume at progression, dt- days to progression), which models tumor volume as increasing exponentially over time. Median growth rates in the treatment and control arms were compared. RESULTS The median growth rate was lower in the treatment arm than in the control. (control: 0.14±0.12 mL/month, TTFields -0.011±0.11 mL/month, p< 0.008 Wilcoxon rank-sum) DISCUSSION AND CONCLUSIONS This study shows that tumor growth rates are slower in patients treated with TTFileds+Temozolomide (TMZ) than in patients treated with TMZ alone. This analysis was restricted to biopsy-only patients since the definition of tumor volume is ambiguous in patients that underwent resection since a large portion of the tumor has been removed. The negative median growth rate for patients in the treatment arm may indicate that a significant number of TTFields-treated patients a decrease in tumor volume was observed, suggesting that TTFields enhances local tumor control. References: [1] Stupp, Roger, et al. Jama 318.23 (2017): 2306–2316.[[2 Stensjøen, Anne Line, et al. Neuro-oncology 17.10 (2015): 1402–1411.

Are Growth Parameters Estimated from Tagging and Age–Length Data Comparable?

1988 ◽  
Vol 45 (6) ◽  
pp. 936-942 ◽  
Author(s):  
R. I. C. C. Francis
Keyword(s):  
Growth Rate ◽  
Growth Rates ◽  
Growth Parameters ◽  
Growth Models ◽  
Maximum Length ◽  
Fish Growth ◽  
Data Sets ◽  
Von Bertalanffy ◽  
Length Data ◽  
The Mean

The two most common ways of estimating fish growth use age–length data and tagging data. It is shown that growth parameters estimated from these two types of data have different meanings and thus are not directly comparable. In particular, the von Bertalanffy parameter l∞ means asymptotic mean length at age for age–length data, and maximum length for tagging data, when estimated by conventional methods. New parameterizations are given for the von Bertalanffy equation which avoid this ambiguity and better represent the growth information in the two types of data. The comparison between growth estimates from these data sets is shown to be equivalent to comparing the mean growth rate of fish of a given age with that of fish of length equal to the mean length at that age. How much these growth rates may differ in real populations remains unresolved: estimates for two species of fish produced markedly different results, neither of which could be reproduced using growth models. Existing growth models are shown to be inadequate to answer this question.

scholarly journals Retrosigmoid Approach for Vestibular Schwannoma

2018 ◽  
Vol 80 (S 03) ◽  
pp. S271-S271
Author(s):  
Mohammed Aref ◽  
Katherine Kunigelis ◽  
Stephen P. Cass ◽  
A. Samy Youssef
Keyword(s):  
Vestibular Schwannoma ◽  
Tumor Resection ◽  
Internal Auditory Canal ◽  
Hearing Preservation ◽  
Neck Surgery ◽  
Cochlear Nerve ◽  
Management Options ◽  
Suppurative Otitis Media ◽  
History Of ◽  
The Right

Vestibular schwannoma is a benign tumor that affects 3% of the population, but accounts for 85% of tumors occurring at the cerebellopontine angle (CPA). In this case, we present a 48-year-old female with history of cholesteatoma on the right and chronic suppurative otitis media on the left who presented with an 18 month history of bilateral hearing loss, worse on the right. Investigations revealed a right sided vestibular schwannoma measuring 1.6 cm in diameter. Audiogram revealed an AAO–HNS (American Academy of Otolaryngology–Head and Neck Surgery) class C hearing on the right and class B on the left. There are several management options for this size of vestibular schwannoma including observation and radiosurgery. However, preserving cochlear nerve function remains a challenging enterprise. Furthermore, the ideal management that confers the highest chance of hearing preservation remains heavily debated. Given the patient's young age, the goal of hearing preservation and the tumor size/extension into the CPA, surgery was decided through a right retrosigmoid transmeatal approach for tumor resection with intraoperative brain auditory evoked responses monitoring. For hearing preservation, we emphasize few important dissection techniques: tumor debulking from the top first to avoid early manipulation of the cochlear nerve at the bottom of the tumor, sharp dissection from medial to lateral off the vestibular nerve which is kept intact as a tension band to minimize cochlear nerve manipulations, and limit the drilling of the posterolateral wall of the internal auditory canal (IAC) medial to the labyrinth and endolymphatic apparatus. Postoperatively, the patient was discharged home within 2 days, with imaging showing a gross total resection. Follow-up audiogram shows unchanged pure tone thresholds.The link to the Video can be found at: https://youtu.be/Z5ftkpJN5k8.

A Practical Application to Calculating Corrosion Growth Rates by Comparing Successive ILI Runs From Different ILI Vendors

2010 ◽  
Author(s):  
Kevin Spencer ◽  
Shahani Kariyawasam ◽  
Cathy Tetreault ◽  
Jon Wharf
Keyword(s):  
Growth Rate ◽  
Growth Rates ◽  
Management Program ◽  
Management Decision ◽  
Pipeline System ◽  
Data Sets ◽  
Simple Method ◽  
Integrity Management ◽  
Inspection Data ◽  
Over Time

Corrosion growth rates are an essential input into an Integrity Management Program but they can often be the largest source of uncertainty and error. A relatively simple method to estimate a corrosion growth rate is to compare the size of a corrosion anomaly over time and the most practical way to do this for a whole pipeline system is via the use of In-Line Inspection (ILI). However, the reported depth of the anomaly following an ILI run contains measurement uncertainties, i.e., sizing tolerances that must be accounted for in defining the uncertainty, or error associated with the measured corrosion growth rate. When the same inspection vendor performs the inspections then proven methods exist that enable this growth error to be significantly reduced but these methods include the use of raw inspection data and, specialist software and analysis. Guidelines presently exist to estimate corrosion growth rates using inspection data from different ILI vendors. Although well documented, they are often only applicable to “simple” cases, pipelines containing isolated corrosion features with low feature density counts. As the feature density or the corrosion complexity increases then different reporting specifications, interaction rules, analysis procedures, sizing models, etc can become difficult to account for, ultimately leading to incorrect estimations or larger uncertainties regarding the growth error. This paper will address these issues through the experiences of a North American pipeline operator. Accurately quantifying the reliability of pipeline assets over time requires accurate corrosion growth rates and the case study will demonstrate how the growth error was significantly reduced over existing methodologies. Historical excavation and recoat information was utilized to identify static defects and quantify systemic bias between inspections. To reduce differences in reporting and the analyst interpretation of the recorded magnetic signals, novel analysis techniques were employed to normalize the data sets against each other. The resulting uncertainty of the corrosion growth rates was then further reduced by deriving, and applying a regression model to reduce the effect of the different sizing models and the identified systemic bias. The reduced uncertainty ultimately led to a better understanding of the corrosion activity on the pipeline and facilitated a better integrity management decision process.

scholarly journals Minimal Effect of Bevacizumab Treatment on Residual Vestibular Schwannomas after Partial Resection in Young Neurofibromatosis Type 2 Patients

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1862 ◽  
Author(s):  
Isabel Gugel ◽  
Lan Kluwe ◽  
Julian Zipfel ◽  
Christian Teuber ◽  
Marcos Tatagiba ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Volume ◽  
Neurofibromatosis Type ◽  
Hearing Preservation ◽  
Neurofibromatosis Type 2 ◽  
Partial Resection ◽  
Vestibular Schwannomas ◽  
Minimal Growth ◽  
Bevacizumab Treatment

Hearing-preserving partial resection of neurofibromatosis type 2 (NF2) associated vestibular schwannomas (VS) is a preferred treatment strategy, particularly for children and adolescents. However, the residual tumors do grow and lead at some point to continued hearing deterioration. An adjuvant bevacizumab treatment may provide an option for slowing down this process. In this retrospective study, we reviewed tumor volume and hearing data of 16 operated VS in nine patients younger than 30 years over a period of 63 to 142 months. All these patients had one or more bevacizumab treatment periods and most of them had a non-treatment period after surgery. Four different patterns of growth were observed for the residual tumors: (1) growth in the non-treatment periods, which slowed down in the treatment periods; (2) growth slowed down in one but not in another on-period; (3) unaffected growth; (4) no or minimal growth regardless of the treatment. Neither radiological regression of tumor volume nor hearing improvement were observed in the treatment periods. Accelerated hearing deterioration was observed in several non-treatment periods, but also in some treatment periods. No straightforward correlation can be drawn between tumor growth and hearing scores. Tumor growth and worsening of hearing between two measurement points were slightly less in the treatment periods; however, the differences were not significant, because variations were large. In conclusion, our comprehensive follow-up on 16 VS in nine NF2 patients did show heterogenous effects of bevacizumab on small residual vestibular schwannomas after surgery both regarding tumor size and hearing preservation. Thus, smaller and slower growing tumor residuals seem to behave differently to bevacizumab than reported for not-operated faster growing VS.

Obtaining Corrosion Growth Rates From Repeat In-Line Inspection Runs and Dealing With the Measurement Uncertainties

2008 ◽  
Author(s):  
Maher Nessim ◽  
Jane Dawson ◽  
Rafael Mora ◽  
Sherif Hassanein
Keyword(s):  
Growth Rate ◽  
Measurement Error ◽  
Measurement Uncertainty ◽  
Growth Rates ◽  
Data Sets ◽  
Field Investigations ◽  
Sample Data ◽  
Integrity Management ◽  
Essential Input ◽  
Measurement Uncertainties

The ability to accurately determine the rate of corrosion growth along a pipeline is an essential input into a number of key integrity management decisions. For example, corrosion rates are needed to predict pipeline reliability (probability of failure and/or probability of exceedance) as a function of time, to identify the need for and timing of field investigations and/or repairs and to determine optimum re-inspection intervals to name just a few applications. As more and more pipelines are now being inspected using intelligent in-line inspection (ILI) tools for a second or even third or fourth time, pipeline operators require reliable guidelines for comparing repeat ILI data sets to obtain valid corrosion growth rates. Because of the measurement uncertainties associated with corrosion size estimated from a single ILI run, the corrosion growth rate calculated from consecutive ILI runs has a degree of uncertainty that needs to be considered in determining valid and accurate corrosion growth rates. The ratio between the measured corrosion growth and the measurement error is an important parameter in determining a meaningful distribution of the corrosion growth rate either when performing defect to defect comparisons or when comparing the defect populations in pipeline segments. When this ratio is small the associated uncertainty can be too large to make meaningful probabilistic inferences. As the ratio increases, the effect of measurement uncertainty becomes more manageable, allowing growth rate distributions to be calculated with reasonable confidence. This paper describes an approach to define the probability distribution of corrosion growth rates as a function of a simple parameter that characterizes the ratio between the ILI-observed corrosion growth and the ILI measurement error. This approach has been developed as part of an ongoing PRCI-sponsored research project to produce procedures for determining and validating corrosion growth rates from repeat ILI runs. The paper also provides examples using sample data from repeat ILI runs showing the application of these procedures, the treatment of measurement uncertainty, the resulting corrosion growth rate information that can be obtained and the associated level of confidence in the results.

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