Our Experience with “Wait and Scan” Protocol in Treatment of Vestibular Schwannoma

Summary

Study objectives:

Most vestibular schwannomas (VS) grow very slowly, only some of them grow rapidly. Observation is a strategy with selected patients. The aim is to evaluate strategy Wait and Scan.

Patients and Methods: In the period 1999-2016, 86 patients with VS were diagnosed. There were 24 patients (28%) were treated surgically, 33 patients (38%) were treated with Leksell Gamma Knife. 29 patients (34%) were indicated for „Wait and Scan“ Protocol. Of these 29 patients, 18 patients were monitored for a long time (follow-up period average of 6 years). Reasons for observations included tumour volume, stage I (61%), advanced age (17%), patient preference (17%), poor health condition (5%). Data on one-year monitored VS were evaluated retrospectively.

Results:

Observations period 2 – 17 years, 6 years in average. 11 patients (61%) were successfully observed without the need for conversion to active treatment, 7 patients (39%) ultimately required active treatment within a mean interval of 3.5 years since diagnosis. 9 tumours (50%) did not grow and 9 tumours (50%) increased their volumes during the observations (2 patients still observed - because of high age and the patient‘s wishes). The average year-on-year rate of tumor growth during the annual follow-up was significantly higher statistically (p=0.01 and 0.05) in the group requiring conversion to an active approach rather than in the group of observed patients. Significant tumour growth was observed up to 5 years after diagnosis, a later VS growth has not been reported.

Conclusion:

Observations of VS is a rational strategy for carefully selected patients. The growth rate of the tumour during the annual follow-up was a strong predictor of the potential need for a proactive approach to treatment. Attention should be paidto the identification of fast-growing and progressive VS, as these must be identified in time and possibly indicated them for active treatment.

Keywords:

vestibular schwannoma, tumour growth, observations, conservative approach

INTRODUCTION

Vestibular schwannoma (VS) is an intracranial extra axial benign tumour stemming from the ectoderm of the Schwann sheath of the vestibular portion of the eighth cranial nerve. Most VS stem from the Schwann cells of the vestibular portion n.VIII. Less than 5% stem from its cochlear portions. VS growth rate varies; according to their grow, VS can be divided into three groups (23) :

• group 1 includes tumors that do not grow, or grow very slowly, 6% of them even reducing their volume,
• group 2 consists of VS growing slowly at around 2 mm a year,
• group 3 is made up of fast growing tumors, growing at 10 mm a year.

Some VS can even double their volume in 6 months. 75% of VS grow very slowly and regularly and only 10% grow rapidly (2). In practice, VS biological activity might be difficult to detect. Some VS behave as described above, others, however, can change their growth characteristics. Thus, VS behaviour cannot be estimated precisely. VS behaviour does not even correspond to histopathological analysis. There are no laboratory methods of determining VS behaviour. Particularly the VS showing cystic degeneration due to blood circulation disturbances can change their dimensions fairly quickly as a result of the rapid growth of the cystic component (2, 23). As VS grow from the Schwann cells of the vestibular portion n. VIII. the tumor first grows trough these fibres. However, the vestibular fibres destruction is slow and gradual, which is why the patients experience almost none or minimal problems with stability. When VS fills the internal auditory meatus, it continues to grow in the area of the internal auditory canal or begins to grow into the cerebello-pontine angle (CPA).

VS first fills the free space of the internal auditory meatus and CPA, and only then does it begin to manifest itself clinically by one of four mechanisms (2,23):

• compression or nerve damage,
• compression of the blood vessels,
• compression of the brain stem,
• disorders of the cerebrospatial fluid flow.

As CPA is a relatively empty space, the tumors can grow up to the size of 3-4 cm before touching the critical structures. VS growth can be so slow that the facial nerve adapts to the tumour pressure and reduces its volume without limiting its function. VS filling the inner ear canal tend to have earlier clinical symptoms, as they oppress the cochlear nerve, vestibular nerves or a. labyrinth against the bony part of the inner ear canal (1,2). When tumors in the cerebello-pontine angle exceed 2 cm diameter they begin to touch the brain stem. A further growth is possible only with the compression or dislocation of the brain stem to the contralaterally. Tumors sized 3 cm growing mainly rostrally touch and oppress n. V. thereby causing its potential malfunction. Further, the tumor with its caudal growth can affect the function of the lateral mixed system. The VS growth beyond 4 cm often results in cerebrospinal fluid distribution failure. Biochemical properties of the tumor alone often participate in the hydrocephalus pathogenesis. Untreated VS is potentially lethal, with brain stem oppression, hydrocephalus and death occuring, according to the published data, after 5 to 15 years of the tumour growth (2, 14, 23).

Monitoring patients with this diagnosis – the “Wait and Scan“strategy – is based on the knowledge that VS is a tumor that grows very slowly. VS losing their growth activity have also been reported. Patients in this group are monitored very closely and they undergo regular checkups, of which magnetic resonance imaging (MRI) is the most important. The checks are carried out usually every 6 to 12 months and then at annualy/yearly intervals. If the clinical status changes, the MRI is performed sooner. The patient´s hearing, the vestibular apparatus as well as other neurological functions are further monitored using audiometric tests. This group consists mainly of patients with small tumors, particularly if their hearing is good. Patients with only one hearing ear, where the tumor is on the side of the hearing ear, older patients, patients with another treatment contraindications, and those who did not prefer an active approach (7,14). It is estimated that 15% to 40% of the patients in this group will have to be treated differently. During the observations, however, about a half of the patients lost the opportunity to be treated actively while having their hearing preserved (4, 5, 16).

STUDY OBJECTIVES

The research analyzed criteria for selection, clinical results and tumor growth in patients diagnosed with VS, where the strategy of observations was the method of choice.

PATIENTS AND METHODS

In the period 1999 - 2016, 86 patients with VS were diagnosed in our department. 24 patients (28%) were primarily operated on. 33 patients (38%) were primarily treated using a Leksell Gamma Knife (LGK). 29 patients (34%) were included in the Wait and Scan Protocol. 11 patients could not be included due to short-term monitoring.

In our retrospective study we observed (for more than 24 months) unilateral vestibular schwannoma in 18 patients, 10 male, 8 female, aged 35 to 82 years, mean age 57 years.

To assess the tumor size and grading, we used an older, but still largely used Koos classification (in collaboration with radiodiagnostics):

• Grade I tumors fill / grow in the internal auditory canal (intracanalicular) only
• Grade II tumors extend into the cerebellopontine angle, but do not reach into the brainstem (up to 2 cm)
• Grade III tumor fills the entire cerebellopontine angle (up to 3 cm)
• Grade IV tumor displaces the brainstem and adjacent cranial nerves (over 3 cm)

Presently, more modern Staging Systems for vestibular schwannomas are also used (Samia, Jackler, Ojemann, Sekhar, Sterkers, CPA maximum diameter) (9).

Follow-ups including MRI were performed annually. MRI was performed using GE Discovery MR 450 1.5 T, GE Signa HDx 3.0 T and GE Signa Excite 1.5 T instruments, with standard examination protocol in three planes in T2 and T1 weighted sequences (layer thickness 5 mm), the diffusion-weighted sequence (B 1000) and 3D FIESTA sequence (layer thickness 0.6 mm). Gadolinium contrast agent had always been administered intravenously during the admission examination. Tumor dimensions were measured on three mutually perpendicular axes and the results were evaluated by a radiologist/ neuro-radiologist. Tumor dimension increase on a single of the three axes was considered as tumour growth progression. Tumor growth was defined as more than 2 mm linear difference in any plane between the diagnostic MRI-scan and the last available scan (21).

The selection criteria for observations were:

• small tumors - VS I and VS II especially with good hearing,
• patients in poor health,
• old patiens,
• patient‘s wishes.

Information on the patiens was presented on annual interdisciplinary seminar where further steps were proposed – observations or active approach, depending on the patient´s clinical state, pure tone audiometry, speech audiometry, videonystagmography, posturography and MRI result.

The rate of tumor growth was observed at annual monitoring, and the tumor growth gradient was a matter of importance to determine whether the tumor growth gradient is a strong predictor of the potential need for a proactive approach to treatment. In the case of proactive approach, a conversion to microsurgery or radio-surgery treatment followed.

The information on the group of 27 patients treated proactively by radio-surgery was reported by the present authors in 2013 and 2014 (4, 5).

RESULTS

Of the total 86 diagnosed VS, 29 VS (34%) were included in the Wait and Scan Protocol. 18 patients with unilateral VS were monitoredin the long term, with observations period 2 – 17 years, 6 years in average.

VS volume (Koos´ Classification):

• degree I. - 11x (61%),
• degree II. - 4x (22%),
• degree III. - 2x (11%),
• degree IV. - 1x (6%).

11 patients (61%) were observed without conversion to an active approach.

This group included an 82-year old patient with VS IV, which grew by 5 mm during the annual follow-up. The patient was further observed due to the old age and generally poor health. The finding was consulted with a neurosurgeon.

Furthermore, a 59-year old female patient with VS I was included in this group. Her tumor suddenly increased by 7 mm after 5 years of observations (her hearing loss deteoriated from Grade II to Grade III of Gardner Robertson Scale), and by another 2 mm after 2 more years. The patient wished to be monitored further. The patient was certainly indicated for conversion to active treatment, however, she has been further observed following her express wish, while no continued tumor growth has been recorded for the previous 2 years.

Conversion to active treatment in 7 patients (39%). Conversion to radio-surgery (Leksell Gama Knife) – 4 patients (22%). Conversion to microsurgical management – 3 patients (17%). Conversion to active treatment was 1 to 5 years from the start of monitoring, the average being 3.5 years.

Significant growth of VS (over 2 mm /year) was observed in 4 patients after one year, in 2 patients after 2 years of observations, in 2 patients after 3 years and in 2 patients after 5 years of observations. All VS showing a significant growth started to grow within 5 years after the diagnosis.

The tumor VS I growth was observed in 6 patients out of 11 (55%), 3 patients were up to the size of VS II, 2 patients up to VS III. Tumor VS II growth observed in 1 patient out of 4 (25%). Tumor VS III growth in 1 patient out of 2 (50%). Tumor VS IV growth in 1 patient out of 1 (100%). The biggest annual VS growth by 9 mm was observed in 2 female patients (11%) after 2 and 3 years from the start of the observations. A spontaneous decrease in VS volume by 2 mm was observed in 2 female patients after 3 years and by 6 mm after 4 years from the start of the observations (11%).

STATISTICAL EVALUATION

A non-parametric test Mann-Whitney was used to test:

1. The tumor volume in each monitored year – values of tumor volume were significantly different between the groups in the 2nd, 3rd and 4th year of monitoring, but only at a significance level of 0.1. The difference statistically significant at level 0.05 is in the 5th year of monitoring (Graph 1).
2. The tumor volume difference between two consecutive years – values of the annual tumor volume change in year 1 – 0 (p=0.01), in year 2 – 1 and 3 – 2 (p=0.05) are statistically significant between the groups on the level of significance 0.01 and 0.05 (Graph 2).

DISCUSSION

Numerous studies have demonstrated that simple but careful observation of these benign and generally slow-growing processes is justified in asymptomatic tumors up to 2.5 cm in size posing minimal risk for the facial nerve and hearing functioning (9).

Our study involves at least two topics to be discussed. A surprising finding of 55% growth of small tumors in the Grade I group: in two patients, growth from Grade I to Grade III was found.

Another unexpected finding was the growth of a small Grade I tumor by 7 mm as late as after 5 years (along with hearing deterioration from Grade II to Grade III of Gardner Robertson Scale), and by further 2 mm in another year. The patient was indicated for conversion to active treatment but was further observed following her express wish, while no continued tumor growth was recorded for another 2 years.

The Wait and Scan approach is described as a many years old modality in the observation of patients with VS (degree I, II Koos´ Classification). The Protocol Wait and Scan is not a modality of treatment but its objective is to identify the very small group of VS with a fast dynamics of growth. The fast growing VS have not only functional clinical impacts /tinnitus, hearing loss, vertigo/ but a further affliction of the central nervous system can take place /VS degree IV Koos´Classification/. This factis particularly expressed in rare malignant forms of VS. Our question was whether the 1 - year interval of MRi scan is a sufficiently frequent examination for the identification of fast growing (or malignant forms) of VS. The analyse of large groups of results indicate that this observation protocol used for VS has been sufficient over there thirty years. The most recent work is fromVanderbilt University by Hunter et al. To date, this is the largest series of observed VS reported in the literature. Risk of VS growth is significantly increased among patients who present with larger tumors. A total of 1296 patients (199 - 2015) with VS were identified. Of those, 564 patients were initially observed and underwent multiple MRI studies (median follow-up 22.9 months). The median maximum tumor diameter at presentation was 1.00 cm (IQR 0.6-1.51 cm). In all, 40.8% of tumors demonstrated growth and 32.1% underwent intervention (21.5% microsurgery, 10.5% radiation) during the surveillance period. Multivariable Cox regression analysis showed that for each tumor, the risk of growth or intervention was significantly increased for larger initial VS diameters (6).

Canadian otolaryngologists observed a tumor growth by about 2 mm in 78% of his patients (3).

Authors from Denmark describe in their report an 82% growth among 123 patients with vestibular schwannoma during the average monitoring period of 3.8 years, no growth in 12% and a spontaneous decrease in volume in 6% of patients (7).

Team of U.S. scientists from Chicago reported a group of 53 patients monitored for 13 years with an average annual neuroma increase by 1.6 mm (0 – 1.64 cm), and 36 patients were recommended an operation (20).

Neurosurgeons from Mayo Clinic (3) observed a growth in 29% of patients and 15% of patients had to undergo surgery treatment within the average period of observation of 3.4 years after the diagnosis of vestibular schwannoma. The average growth in the whole group was 0.72 mm during the first year of monitoring, the growth was 3 mm in the group to be operated on, and there was no spontaneous regression of the tumour. Following a partial removal of the vestibular schwannoma, Japanese neurosurgeons (10) observed a group of 19 patients 5 – 17 years after the surgery treatment (median 10 years) and 53% had the growth continued, 32% had no change and 16% showed signs of tumour regression. 26% of the patients required repeated surgery. A more rapid growth was observed in five neuromas with a cystic component, the period of doubling the volume was 0.15 – 5 years (median 4.5 years),

in five solid residues the time of doubling the volume was 9 to 34 years (median 15 years).

Specialist neurosurgeon from U.S.A. (22) monitored a group of 90 patients for VS growth which was registered in 58% of the patients at 3.4 mm a year. 20% of the patients had to be recommended a surgery treatment within 1.5 year from the diagnosis where the VS growth was by 8.4 mm, and a maximum of 17 mm.

The authors from Sweden (15) monitored 93 patients for between 1 and 15 years and he reported that the VS increase occurred in 66% of the patients between the first and second year after the diagnosis, between the third and fourth year the growth occurred in 86% and if the patients were monitored for more than 3 years the growth occurred in all patients.

American ear researchers from Florida (19) and the team of radiologists from Finland (11) observed a more rapid growth: by 2.5 and 4 mm a year.

The growth rate can be slower in older patients by an average of 1.4 mm a year (17). Other authors deny the difference in the tumor growth rate depending on age (18).

It follows from the above that the growth of vestibular schwannoma can be considerably variable. If the strategy of “Wait and Scan“ was chosen, a check-up examination using MRI is desirable at least once a year for an early detection of the potential tumor growth (8, 13). This requires appropriate availability and capacity of the necessary examination methods. Their limited availability could result in sporadic checks and long intervals with an increased risk of considerable tumour progression.

Czech specialist in the treatment of Leksell gamma knife (12) considers the “Wait and Scan“ strategy for a large proportion of patients,especially the -young ones, as an unnecessary delay of the treatment until the time when the tumour is larger and the prospect of non-complicated course of treatment is less. Early treatment is thus generally better for the patient than observation and waiting for worsening the clinical state (12).

According to leading Czech neurosurgeon - a specialist in surgery of vestibular schwannoma (9, 23) monitoring and repeated examining (particularly of hearing and MRI of brain) is justified so as to determine whether a particular VS belongs among the growing ones. This, however, applies only to tumours VS I and VS II. Tumours that do not grow are just monitored. On the other hand, tumours of the groups VS III and IV, growing tumours and those which affect clinical symptoms, such as hearing inadequacy progress or brain stem symptoms should be treated (9, 23).

The fact that the care (in Czech Republic) of the patients with VS is not centralized is a serious problem, there is no central register of patients with VS, and inter-institutional cooperation is often missing.

Most medical workplaces have small groups of patients with VS and that is why identification of risk patients with growing VS is difficult. In common practice these are, however, individual cases but statistically it is a matter of some 30% of patients with VS. In Czech Republic,the only results and statistical data of the Wait and Scan Protocol have been published from the ENT department University Hospital Motol (1). Thirty-nine patients had undergone observation. The mean duration of follow-up was 67 months (range, 14–127 months). The majority of tumors showed a minimal but definitive growth of 0.1–1 mm per year. Spontaneous regression was observed in 10% and significant growth was observed in 23% of cases. Hearing deterioration (48%) occurred irrespective of tumor growth. Significant growth, worsening of useful hearing, and new symptoms led to a change of treatment strategy in 26% of patients (1).

CONCLUSION

The VS growth potential has not been described so far from the view point of time. Such characteristic has not been examined from the view point of tumour genetics. Neurootologists (otorhino-laryngologists) are usually the first physicians who come a cross the VS clinical diagnosis. This is the reason why they indicate and include the patient into the Wait and Scan Protocol or they indicate the patient for active treatment. Two types of patients can be included in the Wait and Scan Protocol – the first type with a slow-growing VS (a correct indication for observation), and the second type with fast growing VS. 20 % of the observed patients show a critical growth changing the treatment strategy already after the first year of observation. The clinic apparently must pay attention to the fast growing and progressive VS and seek ways and mean show to identify the more indicate them for active treatment.

VS observation is a reasonable strategy for carefully selected patients with VS (degree I and II). Regular follow-up is recommended once a year including MR as certain tumours grow in volume and they require proactive management. Significant tumour growth was observed up to 5 years after diagnosis, a later VS growth has not been reported.

Acknowledgements

The authors thank ing. Alena Dohnalová for her valuable assistance in data analysis.

Conflict of interest statement

The authors state that there are no conflicts of interest regarding the publication of this article.

This research was supported by the Ministry of Defence of the Czech Republic, MO 1012 Research Project.

Adresa ke korespondenci:

As. MUDr. Richard Holý, Ph.D.

Klinika ORL a maxilovaciální chirurgie

3. LF UK a ÚVN Praha

U Vojenské nemocnice 1200

169 02  Praha 6

e-mail: richard.holy@uvn.cz