gms | German Medical Science

The vestibular schwannoma (VS) is a benign neoplasm originating from the neurolemmal sheath of the vestibular branch of the VIIIth cranial nerve. The majority of VSs (95%) appear sporadic and unilateral and are present in the fourth to sixth decades of life. In 5% of patients VSs may also occur in neurofibromatosis Type II, a dominantly inherited syndromic disease. Improved imaging techniques, in particular magnetic resonance imaging (MRI) with gadolinium enhancement, have enabled the diagnosis of VS at very small size. Besides the surgical removal of the tumor, radiation therapy is an alternative treatment option, in particular for small or medium-sized VSs and recurrent tumors [Ref. 1]. Moreover, conservative management (“wait-and-scan” policy) is increasingly common, especially in patients with high operative risk and/or small tumors with minimal symptoms. Decisions about the therapy option could benefit from a better understanding of biological and clinical behaviour of VS and the conditions that influence tumor growth. Therefore, the present study was undertaken to determine the clinical growth index of a series of 118 unilateral VSs and investigate whether VS growth, tumor size, symptoms and symptom duration are related to tumor localization and patient sex and age.

Study group: A retrospective case review of 118 patients with a diagnosis of sporadic unilateral VS was conducted.

Scanning technique and image analysis: Imaging was performed on a 1.5 Tesla MR scanner. Measurements of tumor size were undertaken with high resolution MRI using 2–3 mm slices. The maximum antero-posterior (A-P) tumor diameter was calculated with a micrometer on the alternator by neuroradiologists.

Clinical growth index: The length of clinical history was estimated from the appearance of the first symptoms and determination of the diagnosis by imaging methods. The clinical growth index was calculated as follows:

where md is the maximum tumor diameter in mm and t is the length of the clinical history in months. The clinical growth index is given in mm/yr after Cardillo et al [Ref. 2].

Patient age and sex: The group comprised 51 women and 67 men, aged 19 to 77 years at the time of surgery (mean age, 53.9±12.9 years).

Tumor localization and diameter: VS localization was described as intrameatal in 46 (IT group), intrameatal and extrameatal in 60 (IET group), and extrameatal in 12 patients (ET group). VS diameter ranged from 3 to 40 mm (mean size, 14.3±7.6 mm). The maximum tumor diameter was significantly larger for the IET group (17.9±6.5 mm) and the ET group (19.3±8.5 mm) than for the IT group (8.5±4.3 mm) (p<0.001, r=0.605).

Clinical growth index: The mean clinical growth index was determined as being 31.3±55.7 mm/yr and ranged from 0.3 to 300 mm/yr for the total group. A significantly lower clinical growth index could be found for the IT group (14.7±25.3 mm/yr) compared with the IET group (41.9±69.2 mm/yr) and the ET group (43.3±52.4 mm/yr) (p=0.031, r=0.206).

Correlation between clinical growth index, tumor size, symptoms, symptom duration, tumor localization and demographic data: A significantly negative correlation between the clinical growth index and the age of the patients could be noted for both the total group (p=0.010, r=–0.244) (Figure 1 [Fig. 1]) and the IET group (p=0.017, r=–0.318). A significantly negative correlation between the maximum tumor diameter and the age of the patients was determined for the ET group (p=0.22, r=–0.676). No relationship could be demonstrated between the symptom duration and the patients’ sex neither in the total group nor in any subgroup.

VS growth, growth rate and growth patterns are of great interest and may contribute to a comprehensive understanding of biological and clinical behaviour of this neoplasm. Especially the choice of therapeutic strategy requires a method to allow the identification of patients with progressive and rapidly growing tumors. A convenient and commonly used method to estimate tumor growth rate is the clinical growth index. This method provides a very attractive alternative to formal radiological growth assessment on serial CT or MRI scans because the clinical growth index can be calculated for an individual scan at the time of diagnosis and does not need any follow-up period.

This measure has been used and described in detail previously by numerous authors [Ref. 2], [Ref. 3], [Ref. 4], [Ref. 5]. Based on the assumptions that the tumor presents an approximately linear growth rate and that the length of symptoms reflects the time the tumor has been growing, the clinical growth index is calculated as the ratio of tumor size and symptom duration. One essential weak point of the clinical growth index is the fact that the length of time over which patients report having clinical symptoms is a subjective measure and therefore shows a high level of interindividual variability. A further often criticized aspect of this estimate of VS growth rate is that the first presentation of symptoms may be influenced by several variables, especially by the tumor localization. This is the first study that considers localization of the VS when analyzing the relationship of the clinical growth index, the tumor size, symptoms and the duration of symptoms to patient sex and age. Thus, for statistical analysis the total group of 118 VSs was divided into three subgroups: intrameatal tumors (IT group), intrameatal and extrameatal tumors (IET group), and extrameatal tumors (ET group). Larger sized VSs could be observed in the IET group (17.9±6.5 mm) and the ET group (19.3±8.5 mm) than in the IT group (8.5±4.3 mm). This finding was highly significant (p<0.001, r=0.605) and supports data recently presented by two different groups [Ref. 6], [Ref. 7]. In addition, we found a significantly higher mean clinical growth index amongst the VSs with an extrameatal component (IET group, 41.9±69.2 mm/yr; ET group, 43.3±52.4 mm/yr) compared with the completely intrameatal localized tumors (IT group, 14.7±25.3 mm/yr) (p=0.031, r=0.206). In an MR imaging study Walsh and coworkers [Ref. 6] also found a higher growth rate in extrameatal localized VSs. Our findings may have several possible explanations. These include the following: first, the space outside the internal auditory canal allows tumors to grow much easier compared to tumors located inside the internal auditory canal. Second, a longer duration of asymptomatic tumor growth and/or third, a delay in the onset of symptoms could provide a rationale for the larger tumors observed in patients with a VS located completely or at least partially extrameatal. This hypothesis is supported by our data demonstrating a shorter clinical history for the ET group (24.6±30.6 months) compared with the IT group (36.4±60.7 months). Both a large tumor size and a short symptomatic period result in a high clinical growth index. To further analyze factors associated with the clinical growth index of VS and the tumor size, we correlated these parameters with the patient sex and age. A significantly negative correlation between the clinical growth index and the age of the patients could be noted for both the total group (p=0.010, r=–0.244) and the IET group (p=0.017, r=–0.318). This result indicates a slower tumor progression in the elderly. Moreover, in our series we found significantly smaller tumors in the older population at least for the ET group (p=0.22, r=–0.676). Our findings support previous results of extensive radiological studies using sequential CT or MRI to examine the relationship between age and VS growth rate [Ref. 8], [Ref. 9], [Ref. 10] and VS size [Ref. 7], [Ref. 11], [Ref. 12]. Even though the clinical growth index is an often criticized and unquestionably rather inaccurate measure, our findings support data previously presented by radiological studies showing the correlation of VS growth, tumor size and localization, and even more important, the VS growth and the patient age.

In conclusion, we regard the determination of the clinical growth index as a measure that might help to council patients in selected situations. Our findings might provide an additional rationale for the consideration of the clinical growth index to estimate the growth rate of the tumor. This could be especially useful in patients where no sufficient MRI follow-up is available. Here, the clinical growth index might help for the initial decision on therapy in addition to consider other criteria like the patient’s age, overall health, symptoms, bilateral hearing, tumor size and finally the patient preference.