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A review of treatment modalities for vestibular schwannoma

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Abstract

Vestibular schwannomas are benign intracranial tumors arising from the vestibular nerve. Treatment options include observation, stereotactic radiosurgery, fractionated radiotherapy, and microsurgery. We review the evidence describing efficacy and side-effect profiles of each of these modalities. This was accomplished by outlining the results of published meta-analyses and performing a systematic search of the literature for individual studies published between 2004 and June 2009. Without intervention, 29–54% of tumors will grow and 16–26% of patients require additional treatment, with 54–63% preserving functional hearing. With radiosurgery, only 2–4% require additional treatment and hearing preservation is accomplished in 44–66% of cases. Reviewing contemporary studies, it appears that reduced marginal doses may have decreased morbidity risks associated with radiosurgery without sacrificing efficacy. With fractionated radiotherapy, 3–7% will require additional treatment and hearing preservation is reported at 59–94% of patients, although long-term outcomes are not known. Microsurgery is an alternative for eligible patients, with fewer than 2% requiring additional treatment; however, the risk of hearing loss, facial neuropathy, and other morbidities is relatively high. There are significant limitations with comparing the efficacy and morbidity rates across interventions because of selection bias and confounding factors. Additional prospective comparative trials and randomized studies are needed to improve our understanding of the relative benefits of each modality.

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Acknowledgments

Funding for this project was provided by Gamma Knife of Spokane and a grant from the University of Washington School of Medicine’s Medical Student Research Training Program (MSRTP). We would like to acknowledge Rachel Garman and Michelle Osso as well as the entire Cancer Care Northwest research staff for their contributions to this manuscript.

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Authors and Affiliations

  1. Gamma Knife of Spokane, 910 W 5th Ave, Suite 102, Spokane, WA, 99204, USA

    Benjamin J. Arthurs, Robert K. Fairbanks, John J. Demakas, Wayne T. Lamoreaux, Neil A. Giddings, Alexander R. Mackay, Barton S. Cooke, Ameer L. Elaimy & Christopher M. Lee

  2. University of Washington School of Medicine, Seattle, WA, USA

    Benjamin J. Arthurs

  3. Cancer Care Northwest, 910 W 5th Ave, Suite 102, Spokane, WA, 99204, USA

    Robert K. Fairbanks, Wayne T. Lamoreaux, Ameer L. Elaimy & Christopher M. Lee

  4. Spokane Brain and Spine, 801 W 5th Ave, Suite 210, Spokane, WA, 99204, USA

    John J. Demakas

  5. Spokane Ear Nose and Throat Clinic, 217 W Cataldo Ave, Spokane, WA, 99201, USA

    Neil A. Giddings

  6. Mackay and Meyer MDs, 711 S Cowley St, Suite 210, Spokane, WA, 99202, USA

    Alexander R. Mackay

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Comments

Jean Régis, Michael C. Park Marseille, France

Is there one approach superior to the others in the neurosurgical management of vestibular schwannomas?

Vestibular schwannomas (VSs), also known as acoustic neurinomas historically, are benign neoplasms of Schwann cell origin, occurring predominantly on the vestibular division of the cranial nerve VIII at the oligodendroglial/Schwann cell interface at or within the internal auditory meatus (10). VSs have always frustrated and challenged neurosurgeons for more than 100 years because of their benign nature and potentially significant surgical morbidity and mortality related to the complex anatomy of the cerebellopontine angle. The surgical management of VSs has evolved from the pioneering era of the life-saving procedure by intracapsular removal (1), to the curative era with complete tumor resection (2), then to the era of facial nerve sparing (17). In the 1960s and 1970s, microsurgical revolution led to the development of modern neurosurgical strategies with the middle fossa approach (7) and the translabyrinthine route (6). Yasargil (27) refined the microsurgical technique, emphasizing the importance of the brainstem arterial supply, specifically anterior inferior cerebellar artery, and the need to optimize the preservation of facial nerve function. These technical advances have resulted in a 50% reduction in mortality, a rate of complete tumor removal reaching 85% and a rate of the successful anatomical preservation of the facial nerve approaching 80%.

In recent years, development of new diagnostic modalities such as computed tomography, magnetic resonance imaging (MRI) and auditory evoke potentials has resulted in the drastic decrease in the average size of VS at diagnosis. In addition, multidisciplinary team approach and intraoperative monitoring of cranial nerves VII and VIII have led to the dramatic improvement in clinical outcome, namely operative mortality of around 1%, total tumor removal rate close to 95%, and preservation of facial motor function (House–Brackman grade I or II) in significant portion of cases involving small tumors (Koos class I and II). In some expert hands, the preservation of useful hearing (Gardner–Robertson class I or II) has been demonstrated to be achievable in selected small lesions with very good preoperative hearing. In 1997, Samii and Matthies (23) published a series of 962 patients with tumor control rate of 98%, an impressive functional hearing preservation rate of 39%, with associated mortality rate of 1.1%, and a reasonable complication rate of CSF leak (9%), meningitis (1.2%), hydrocephalus (2.3%) and miscellaneous events (5%).

The most recent neurosurgical advance has been that of radiosurgery. Conceived during the microsurgical revolution of the 1960s and 1970s (11, 12), the fantastic image-guided neurosurgical instrument, which Leksell called the Gamma Knife, has realize its full potential with the appearance of modern imaging in the late 1980s, specifically MRI. In the 1990s, radiosurgery became the first-line treatment option for small- to middle-sized VSs, especially in young patients with few symptoms (9, 14, 16, 21). However, microsurgery still remains as the first-line treatment for large VSs (Koos class IV), which is still challenging. In the twenty-first century, the demonstration of the high rate of functional preservation has led us to promote the idea of a combined microradiosurgical approach for large VSs, allowing a dramatic reduction in the rate of facial nerve palsy in large VSs from 50% to less than 20% (5, 8).

The strategy of “surgical removal at all cost” has evolved into the strategy of “cranial nerve preservation whenever possible”. Currently, the management of this tumor has become less controversial but continues to fascinate generations of neurosurgeons and neuro-otologists. No tumor provides a greater test of a neurosurgeon’s or neuro-otologist’s skill than the VSs. However, the need for improved outcomes proved the driving force in the introduction and development of stereotactic radiosurgery as a potent management strategy. Over the years, cranial nerve function preservation rates have dramatically improved and now hearing preservation is a reality.

Our oto-neurosurgical experience of more than 4,500 VSs has led us to consider that, in the modern era, treatment of VSs should be tailored individually and be managed by experienced multidisciplinary teams able to integrate all the microsurgical and radiosurgical approaches in order to provide the highest level of care, the highest probability of functional preservation, and good quality of life.

Arthurs et al. are providing us with a review of the different treatment options in the management of VSs. The authors are comparing Wait & See, microsurgical resection, radiosurgery, and stereotactic radiotherapy in the management of VSs. They are reviewing papers about these several approaches, which correspond to different populations of patients and use different evaluation criterion. This work is a review of the literature, and it does not present any original data, but is attempting to look broadly at the available data from recent years and compile it into a comprehensive review. There are major flaws in their process, which they have attempted to address in the discussion of the paper. For those interested in the modern management of VSs, this work constitutes a useful review under the condition of a clear identification of its flaws and weaknesses.

1. First, the strategy of the authors was to scrutinize published cohort from a specific time period (2004–2009). The authors have decided to investigate only a sampling of the literature between 2004 and 2009. To analyze only the modern literature, excluding old papers, which may present a technical gap, is sensible. However, the lower limit of 2004 seems very much restrictive and leads the authors to miss some of the more important papers of the modern literature.

2. The heterogeneity among the methodology of different papers reporting their results of the diverse therapeutic strategies is so varied that frequently the authors are performing “forced comparisons”, often leading them to somewhat invalid conclusions. In such a comparison, the rules cannot be changed depending on what technique is evaluated. The efficacy must be defined similarly in Wait & See, Microsurgery, and Radiosurgical populations. For example, Arthur et al. are defining a failure for microsurgery as the requirement for a new surgery (either microsurgery or radiosurgery) and for radiosurgery as a significant tumor growth. Thus, Arthur et al. have decided on different definitions of failure (different rules) for microsurgery and radiosurgery. In radiosurgery, it is a well-known and well-published fact that VSs after radiosurgery frequently increase in size for some time and then stops growing thereafter in long term (in the majority of the patients). Some of the patients with long-term follow-up demonstrating complete arrest of growth for a very long period of time have a tumor that is larger compared to the size before radiosurgery, due to the growth during the first 2 years (3). These patients are clearly considered as “cured” and cannot be considered as failures. Thus, in the abstract, the failure rate of radiosurgery must read 2–4% (success rate 96–98%). Also, the rate of failure after fractionated radiotherapy is 5.4% (2.9–6.7%) and this seems higher.

3. Selection bias is the other major weakness of this review. This is especially true for the comparison of hearing preservation rates, which may not be valid because of the selection of the best responders in the radiotherapy and microsurgery groups. Major patient selection bias is obvious in some papers in the literature and makes any attempts of comparison unfair. Even if, in the papers from micro and radiosurgery literature, the useful hearing preservation rate is calculated for those patients with a useful hearing before the operation, there is a major difference related to the selection of “good candidates” for microsurgical attempt for hearing preservation. Frequently in microsurgical series, the rate of hearing preservation is not defined as the number of patients keeping a useful hearing based on the total number of patients with useful hearing before the surgery but based on the smaller group of patients selected, as good candidate, for an attempt to preserve hearing. In several papers, one of the main criteria is a subnormal hearing (Los Angeles A or Garner–Robertson I). Thus, these specific papers from the microsurgical literature must be compared to the results of radiosurgical papers analyzing the results of radiosurgery in this specific group of patient (26). The young age, which is frequently used as a major selection criterion for an attempt to preserve functional hearing in microsurgical series is also demonstrated to influence the chances for hearing preservation (13). Thus, the rate of hearing preservation, already significantly higher with high precision radiosurgery can be even more favorable when considered in this selected group of “good candidate” patients. Series of fractionated radiotherapy also demonstrate this bias when patients retained for fractionation are those who are young with a small lesion and a very good hearing! Any comparison in terms of functional hearing preservation must take into account these strong predictors and must be stratified.

4. Series with short follow-up may be especially misleading. In Wait & See strategy, the series are small and follow-up short (compared to the slow-growing natural history of these tumors). The number of patient operated because of growth seems modest at 3 years but with an average growth of 1–2 mm a year, the actuarial rate of patient requiring surgery at 5–10 years is much higher. Thus, the high rates of “success” of the Wait & See strategy claimed by some authors in these small series with short follow-up must be viewed with caution. Thus, the following sentence “Without intervention, 29–54% of tumors will grow; however, observation remains successful in that only 16–26% of patients require additional treatment” is unrealistic at the scale of patient life expectancy. These observations must be replaced in the context of a longer time frame. As a minimum requirement, actuarial rates of failure (growth requiring treatment) at 3, 5, and 10 years must be reported. In fact, the true benefit of these management strategies should be theoretically considered at the scale of patient life expectancy. In a recent prospective study evaluating Wait & See strategy in the management of VSs, the actuarial rate of tumor progression was reported (20). Additionally, in Wait & See series, some authors are using syncretic definition of tumor growth. For example, Stangerup et al. are reporting surprisingly only 17% of tumor increase in a group of 230 Koos I tumors with a mean follow-up of 3.6 years (24). In fact, the authors have decided to define as “growing” only tumors that are becoming extrameatal. Thus, for these authors, a small tumor of 2 mm diameter increasing in size to a 14 mm tumor (from 4 to 420 mm3) but still in the canal is considered a non-growing tumor! Finally, the quite high rate of hearing loss with this approach must be mentioned (25). Also, vast majority of series of stereotactic radiosurgery also possess this bias (small series and short follow-up) in addition to the selection bias already mentioned. The claim that fractionated stereotactic radiotherapy may be superior to radiosurgery in terms of functional hearing preservation is, until now, not substantiated by the literature (4). In the only two series of radiotherapy reporting significantly better results of hearing preservation than radiosurgical series (Combs et al. 2005 and Chan et al. 2005) the hearing is not systematicaly evaluated by audiometry before and after but based on patient self assessment.

5. Comparing the results of safety and efficacy of different techniques may be an attempt to answer an inappropriate question since nowadays these approaches are frequently proposed in combination. Especially in large Koos class IV tumors, centers of excellence, benefiting from many modalities and human skills available to them, are increasingly offering a combination of partial removal under physiological monitoring followed by radiosurgery of the remnant. Consequently, these approaches are not intrinsically antagonistic.

The authors obviously have faced a certain number of methodological difficulties. In order to make relevant and valuable comparisons, we need to be sure to compare the similar type of patients and utilize, as much as possible, the same evaluation criterion for the different techniques.

Surprisingly, while regretting the rarity of the comparative studies, the authors do not pay attention to the existing papers reporting such studies (15, 18, 19, 22). There is a total of five such comparative studies in the literature, very convergent in their conclusion and establishing that the functional outcome after radiosurgery is superior as compared to microsurgery in small to moderate size VSs (even if some of these comparative studies predate 2004). Of course, each of these trials has its methodological limits. However, the level of evidence of these studies is much higher than a forced comparison of retrospective non-comparative cohorts from the literature!

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Arthurs, B.J., Fairbanks, R.K., Demakas, J.J. et al. A review of treatment modalities for vestibular schwannoma. Neurosurg Rev 34, 265–279 (2011). https://doi.org/10.1007/s10143-011-0307-8

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