Abstract
Objective
To compare hearing preservation between stereotactic radiotherapy (SRT) and conservative treatment of patients with unilateral vestibular schwannoma.
Data sources
Retrospective case series comparing hearing outcomes of patients with a unilateral vestibular schwannoma managed conservatively or with stereotactic radiotherapy in a tertiary care academic centre.
Review methods
Patients: Tumor database patients with American Academy of Otolaryngology Head and Neck Surgery Class A or B hearing at the onset of study. Stereotactic radiotherapy patients were predominantly those who failed conservative management.
Interventions: Audiometric pure tone averages and speech discrimination scores as well as patient demographics, tumor location, size and growth were extracted.
Main outcome measures: Hearing outcome measures were: 1) Hearing Preservation, i.e. no drop from Class A/B to Class C/D hearing, 2) Hearing Survival of Class A/B hearing in months, 3) Audiometric Pure Tone Averages, Difference between post-treatment and pre-treatment, and 4) Speech Discrimination Score Difference (pre-treatment − post treatment). Survival analysis and non-parametric tests were used for hearing outcome measures, with multiple covariates tested.
Results
Overall, serviceable hearing preservation among the 123 patients was 51%. The median hearing survival time was 46 months (mean 59 months). The Pure Tone averages and Speech Discrimination score differences were 16 dB and 82% respectively over a median follow-up time of 43 months. No significant difference was found between the conservative and SRT groups in any hearing outcome. Class A patients showed far better hearing survival than Class B patients.
Conclusions
No significant difference was demonstrated as to measures of hearing outcomes between stereotactic radiotherapy and conservative management. Excellent existing hearing appears to be the best predictor of long term hearing survival in the cohort studied.
1
Introduction
Vestibular schwannomas (VS) (or acoustic neuromas (AN)) are benign brain tumors arising from the myelin-forming Schwann cell of the 8th cranial nerve (vestibulocochlear nerve). The prevalence of VS is approximately 1 in 1000 persons, with increased incidence due to incidental finding through MRI imaging . VS can cause auditory and vestibular symptoms such as hearing loss, vertigo, and tinnitus; facial symptoms such as paralysis and numbness; and with increased growth life threatening sequelae such as brainstem compression and hydrocephalus.
Clinical management of VS includes conservative management or “wait and scan”, surgery, and/or stereotactic radiotherapy . These treatment strategies vary in their hearing preservation rates. Conservative management entails carefully following the tumor’s growth with serial MRI scans . In many clinics, most tumors are followed by this approach and do not require direct intervention. However, hearing tends to decline with time, even in the absence of tumor growth . Surgical resection is another treatment option. However, surgical resection with hearing preservation, while feasible in very small tumors, has a high likelihood of hearing loss in larger tumors; indeed it is a certainty if the translabyrinthine surgical route is chosen .
Stereotactic radiotherapy (SRT) is an alternate treatment modality which uses multiple beams of radiation converging onto a single target over several sessions in order to deliver a high dose of therapy, while limiting exposure of healthy surrounding tissue to damaging radiation. SRT has been reported to have a success rate of over 95% in controlling growth of VS . However, it is currently unclear whether SRT stabilizes hearing in treated individuals, or actually accelerates hearing loss. At the Maritime Lateral Skull Base Clinic (formerly the Atlantic Lateral Skull Base Clinic) we employ a patient-centered model with all options explained to the patient; which has resulted in most tumors being followed conservatively. However, if a tumor is growing (> 2 mm/MRI scan), and is under 25 mm in diameter, SRT is often considered as the next treatment option. There is, however, a lack of literature focusing on the hearing outcomes of SRT versus conservative wait and watch treatment.
The objective of our study was to compare hearing preservation and hearing survival times of patients undergoing either conservative or SRT treatments in the management of unilateral acoustic neuromas. This is an important question, as if SRT is strongly protective of hearing, it could be offered as a first line treatment option, superseding conservative management. However, if SRT accelerates hearing loss, it might be reasonable to wait longer in the face of mild–moderate tumor growth before offering this modality. Lastly, if SRT has no appreciable effect on hearing, than it would be a reasonable option for patients with small tumors, demonstrating growth on imaging. This finding would affect treatment strategies for patients under the care of the Maritime Lateral Skull Base clinic and other treatment centers involved with the management of VS. We recognize that there is a difference in the two populations in that the SRT group is comprised mostly of growing tumors, whereas the conservative group represents stable tumors. The difference is unavoidable as we do not advocate for SRT in the majority of cases without evidence of tumor growth. In some respects this is encouraging as the sample is comprised of patients where the most reasonable option was SRT, and no change or preservation of hearing would both be favorable outcomes. Surgical patients were not included.
2
Materials and methods
This retrospective case series compared patients with VS who were managed conservatively to patients who either were primarily managed with SRT or who failed conservative management and went on to have SRT. Patient details were extracted, with prior informed consent signed, from the Maritime Lateral Skull Base clinic database. Ethics approval for this study was obtained from our local Research Ethics Board.
2.1
Management protocol
At our center, conservative management predominated for patients with VS using the “wait-and-scan” approach. This included serial MRI scanning and audiometric testing (conservative management) as outlined previously . However, if a tumor was large (> 25 mm), or was growing (> 2 mm/MRI), then active treatments such as surgical or radiotherapy interventions were considered. The present study focused only on the conservative and SRT treatment modalities.
For patients who received SRT, the procedure was performed using a standardized linear accelerator for delivery of stereotactic radiation. Patients received either 3125 cGy in 5 fractions, or in one case 6250 cGy in 25 fractions.
2.2
Patient characteristics
The case series was drawn from a database of 405 patients with VS followed between July 1996 and July 2011 by the Maritime Lateral Skull Base clinic. Excluded were: surgical management (n = 87), having had SRT at another center (n = 16), lack of follow up (e.g. < 2 audiograms) or insufficient data (n = 46), additional brain tumors or uncertain findings (n = 17), neurofibromatosis type II (n = 7) or non-serviceable hearing at onset (AAOHNS class C or D) (n = 109) . Lack of adequate hearing was the major exclusion criterion. The statistical analyses were performed on 123 patients, 98 of whom underwent conservative therapy and 25 whom underwent SRT. In total, there were 62 male and 61 female participants with a median age of intervention of 55 years (range 16–85) and a median follow up time of 43 months (range 3–131). For further descriptive statistics, see Table 1 .
| Sex | |||
| Male | n (%) | 62 | (50%) |
| Female | n (%) | 61 | (50%) |
| Age (years) | |||
| Median (Range) | 55.0 | (16–85) | |
| Tumor location | |||
| IAC | n (%) | 48 | (39%) |
| CPA | n (%) | 75 | (61%) |
| Tumor size | |||
| IAC | n (%) | 48 | (39%) |
| Small | n (%) | 59 | (48%) |
| Medium | n (%) | 16 | (13%) |
| Large | n (%) | 0 | |
| Tumor growth status | |||
| Stable | n (%) | 87 | (71%) |
| Growing | n (%) | 30 | (24%) |
| Shrinking | n (%) | 6 | (5%) |
| AAOHNS hearing class at onset on tumor side | |||
| A | n (%) | 48 | (41%) |
| B | n (%) | 73 | (59%) |
| Decreased hearing on both tumor and contralateral sides | |||
| No | n (%) | 120 | (98%) |
| Yes | n (%) | 2 | (2%) |
| Missing | n (%) | 1 | |
| Follow-up in months | |||
| Median (Range) | 43 | (3–131) | |
| Treatment modality | |||
| Conservative | n (%) | 98 | (80%) |
| SRT | n (%) | 25 | (20%) |
2.3
Hearing assessment
The audiometric protocol has been described previously . Briefly, patient hearing levels were determined by audiometric testing based on speech discrimination scores (SDS) and pure-tone averages (PTAs) of 0.5, 1, 2, and 3 kHz. The American Academy of Otolaryngology–Head and Neck Surgery hearing classification system was used to categorize both pre- and post-treatment hearing levels, with only patients having serviceable hearing (class A or B) at the onset included in the analyses.
2.4
Tumor characteristics
Tumor characteristics were based on location, size, and growth. Tumor size was measured using a protocol previously outlined . One author (A.E.) reviewed all MRI images and calculated tumor size. For cerebellopontine angle (CPA) tumors, size was calculated as the square root of the product of the maximum tumor diameter parallel to the petrous ridge and the perpendicular linear measurement of the extracanalicular portion of the tumor. If the tumor was purely intracanalicular (IAC), a linear measurement was taken parallel to the portion extending the length of the internal auditory canal. Furthermore tumors were classified into size categories: IAC, small (< 15 mm), medium (15–30 mm), and large (> 30 mm) as previously documented . Tumor growth was defined as an increase of > 2 mm on 3–12 month interval MRIs, and tumors were further classified as growing or stable/shrinking .
2.5
Outcome measures
The four outcome measures of interest were:
- 1.
Hearing preservation: hearing status at the end of follow-up with preservation defined as retention of serviceable hearing class A/B, and loss defined as a drop from class A/B to C/D.
- 2.
Hearing survival in months (time spent in class A/B).
- 3.
PTA difference (post-treatment PTA − pre-treatment PTA).
- 4.
SDS difference (pre-treatment SDS − post treatment SDS).
Considered as independent variables were: demographic characteristics (gender, age); tumor characteristics (location, size class, growth); and, possible hearing predictors (AAOHNS hearing class, contralateral ear hearing class, pre-SRT (including contralateral ear) hearing decline, and length of follow up time).
2.6
Statistical analysis
All data were summarized using descriptive statistics. Univariate comparisons were conducted between each of the outcomes of interest and each of the independent variables. Univariate non-parametric tests for binary dependent variables included Chi-square, Fisher’s exact, and Kolmogorov–Smirnoff, while for continuous dependent variables Kruskal Wallis and linear regression were used. Multivariate models were conducted to predict treatment modality and all hearing outcomes. Multivariate tests included logistic regression for binary dependent variables and multiple regression for continuous dependent variables. Survival analysis for hearing preservation in months was conducted comparing Kaplan–Meier survival curves with log rank Mantel–Cox tests, and Cox Proportional Hazards Regression was used to analyze covariates within the model. Results were considered significant at an alpha of 0.05. The statistical software used was SPSS 15.0 (SPSS, Chicago, IL).
2
Materials and methods
This retrospective case series compared patients with VS who were managed conservatively to patients who either were primarily managed with SRT or who failed conservative management and went on to have SRT. Patient details were extracted, with prior informed consent signed, from the Maritime Lateral Skull Base clinic database. Ethics approval for this study was obtained from our local Research Ethics Board.
2.1
Management protocol
At our center, conservative management predominated for patients with VS using the “wait-and-scan” approach. This included serial MRI scanning and audiometric testing (conservative management) as outlined previously . However, if a tumor was large (> 25 mm), or was growing (> 2 mm/MRI), then active treatments such as surgical or radiotherapy interventions were considered. The present study focused only on the conservative and SRT treatment modalities.
For patients who received SRT, the procedure was performed using a standardized linear accelerator for delivery of stereotactic radiation. Patients received either 3125 cGy in 5 fractions, or in one case 6250 cGy in 25 fractions.
2.2
Patient characteristics
The case series was drawn from a database of 405 patients with VS followed between July 1996 and July 2011 by the Maritime Lateral Skull Base clinic. Excluded were: surgical management (n = 87), having had SRT at another center (n = 16), lack of follow up (e.g. < 2 audiograms) or insufficient data (n = 46), additional brain tumors or uncertain findings (n = 17), neurofibromatosis type II (n = 7) or non-serviceable hearing at onset (AAOHNS class C or D) (n = 109) . Lack of adequate hearing was the major exclusion criterion. The statistical analyses were performed on 123 patients, 98 of whom underwent conservative therapy and 25 whom underwent SRT. In total, there were 62 male and 61 female participants with a median age of intervention of 55 years (range 16–85) and a median follow up time of 43 months (range 3–131). For further descriptive statistics, see Table 1 .
| Sex | |||
| Male | n (%) | 62 | (50%) |
| Female | n (%) | 61 | (50%) |
| Age (years) | |||
| Median (Range) | 55.0 | (16–85) | |
| Tumor location | |||
| IAC | n (%) | 48 | (39%) |
| CPA | n (%) | 75 | (61%) |
| Tumor size | |||
| IAC | n (%) | 48 | (39%) |
| Small | n (%) | 59 | (48%) |
| Medium | n (%) | 16 | (13%) |
| Large | n (%) | 0 | |
| Tumor growth status | |||
| Stable | n (%) | 87 | (71%) |
| Growing | n (%) | 30 | (24%) |
| Shrinking | n (%) | 6 | (5%) |
| AAOHNS hearing class at onset on tumor side | |||
| A | n (%) | 48 | (41%) |
| B | n (%) | 73 | (59%) |
| Decreased hearing on both tumor and contralateral sides | |||
| No | n (%) | 120 | (98%) |
| Yes | n (%) | 2 | (2%) |
| Missing | n (%) | 1 | |
| Follow-up in months | |||
| Median (Range) | 43 | (3–131) | |
| Treatment modality | |||
| Conservative | n (%) | 98 | (80%) |
| SRT | n (%) | 25 | (20%) |
2.3
Hearing assessment
The audiometric protocol has been described previously . Briefly, patient hearing levels were determined by audiometric testing based on speech discrimination scores (SDS) and pure-tone averages (PTAs) of 0.5, 1, 2, and 3 kHz. The American Academy of Otolaryngology–Head and Neck Surgery hearing classification system was used to categorize both pre- and post-treatment hearing levels, with only patients having serviceable hearing (class A or B) at the onset included in the analyses.
2.4
Tumor characteristics
Tumor characteristics were based on location, size, and growth. Tumor size was measured using a protocol previously outlined . One author (A.E.) reviewed all MRI images and calculated tumor size. For cerebellopontine angle (CPA) tumors, size was calculated as the square root of the product of the maximum tumor diameter parallel to the petrous ridge and the perpendicular linear measurement of the extracanalicular portion of the tumor. If the tumor was purely intracanalicular (IAC), a linear measurement was taken parallel to the portion extending the length of the internal auditory canal. Furthermore tumors were classified into size categories: IAC, small (< 15 mm), medium (15–30 mm), and large (> 30 mm) as previously documented . Tumor growth was defined as an increase of > 2 mm on 3–12 month interval MRIs, and tumors were further classified as growing or stable/shrinking .
2.5
Outcome measures
The four outcome measures of interest were:
- 1.
Hearing preservation: hearing status at the end of follow-up with preservation defined as retention of serviceable hearing class A/B, and loss defined as a drop from class A/B to C/D.
- 2.
Hearing survival in months (time spent in class A/B).
- 3.
PTA difference (post-treatment PTA − pre-treatment PTA).
- 4.
SDS difference (pre-treatment SDS − post treatment SDS).
Considered as independent variables were: demographic characteristics (gender, age); tumor characteristics (location, size class, growth); and, possible hearing predictors (AAOHNS hearing class, contralateral ear hearing class, pre-SRT (including contralateral ear) hearing decline, and length of follow up time).
2.6
Statistical analysis
All data were summarized using descriptive statistics. Univariate comparisons were conducted between each of the outcomes of interest and each of the independent variables. Univariate non-parametric tests for binary dependent variables included Chi-square, Fisher’s exact, and Kolmogorov–Smirnoff, while for continuous dependent variables Kruskal Wallis and linear regression were used. Multivariate models were conducted to predict treatment modality and all hearing outcomes. Multivariate tests included logistic regression for binary dependent variables and multiple regression for continuous dependent variables. Survival analysis for hearing preservation in months was conducted comparing Kaplan–Meier survival curves with log rank Mantel–Cox tests, and Cox Proportional Hazards Regression was used to analyze covariates within the model. Results were considered significant at an alpha of 0.05. The statistical software used was SPSS 15.0 (SPSS, Chicago, IL).
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