Growth dynamics of the vestibular schwannoma
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Introduction: Studies concerning vestibular schwannoma (VS) are inconsistent in reporting of tumor size and growth. This means that results found in one paper using one set of definitions cannot be compared directly with results found in another paper with another set of definitions. It is a challenge to make clinical decisions from studies with such disparate definitions, as it is difficult to know how reliable the individual findings are. This thesis thus aimed to empirically evaluate these different means of reporting tumor size and growth that can be found in the literature. In addition to this, we also present our own findings of the growth dynamics and predictors of untreated VS, as well as evaluating the treatment outcome and complication rates for tumors treated by gamma knife radiosurgery (GKRS). Methods: The management of VS patients is determined primarily based on the tumor size and observed tumor growth. The smallest tumors are conservatively treated by serial scans, and if growth is detected, they are offered active treatment by either microsurgery or GKRS. The papers in this thesis primarily focus on the conservatively treated cohort, and those among them that were later treated by GKRS. Tumor volumes were estimated by manual tracing on MRI. Mixed effects modeling was used to analyze relationships between observations. Results: The papers included in this thesis present a number of results. The first paper found several inherent flaws with the most commonly used measure, the maximum diameter. Empirical proportionality coefficients which were quite similar to theoretical values used in the literature were also found. The second paper showed that tumor growth was best described by volume doubling time (VDT) rather than in terms of mm/year. We found a VDT of 4.40 years among our cohort. We also discussed the use of a cutoff of 1 mm/year to distinguish between growing and non-growing tumors, and proposed a VDT cutoff of 5.22 years that could be used similarly. None of the baseline parameters investigated were predictive of tumor growth. The third paper described the risk of needing treatment with the wait-and-scan protocol to be 13.3% at two years, and 41.3% at five years. The study also found a decline of hearing function for conservatively managed patients. Neither tinnitus nor unsteadiness changed significantly from baseline, but there was a reduction in the number of patients reporting vertigo. Results also suggest that tumor growth may be associated with progression of tinnitus and imbalance problems. The fourth paper found a radiological tumor control rate of 71.1%. Higher age and larger tumor size were found to be positively associated with tumor control. Hearing was preserved in 79% of the patients who had serviceable hearing at the time of treatment. Permanent facial weakness as a result of GKRS treatment occurred in one patient. In terms of QoL, bodily pain and general health scores improved significantly after GKRS. Social function steadily declined throughout the follow-up period, which may be related to the increasing number of patients experiencing unilateral hearing loss. Conclusion: In the discussion of inconsistencies in reporting of tumor size and tumor growth, our studies propose that there exist both empirical and biological arguments for the use of volumes and VDT’s rather than diameters and linear growth rates. A VDT cutoff of 5.22 years can distinguish between clinically growing and non-growing tumors. Our findings support the continued use of a conservative approach among small, non-growing tumors. For medium-sized or growing tumors, we also suggest that GKRS is a preferable treatment to microsurgery, given the high tumor control rates and low rates of complication with GKRS. The tumor control can also be improved by taking into consideration the potential predictors found in our study when selecting patients for this treatment, namely the patient’s age and the tumor size (although from a radiobiological point of view, one would expect the opposite effect from these parameters). Several scales of QoL were also found to improve significantly after GKRS, thus supporting the practice of recommending this form of treatment to these tumors. The social function scale however got steadily worse from baseline.
Paper I: Varughese JK, Wentzel-Larsen T, Vassbotn F, Moen G, Lund-Johansen M. Analysis of vestibular schwannoma size in multiple dimensions: a comparative cohort study of different measurement techniques. Clinical Otolaryngology 35(2): 97-103, April 2010. Full text not available in BORA due to publisher restrictions. The article is available at: http://dx.doi.org/10.1111/j.1749-4486.2010.02099.xPaper II: Varughese JK, Breivik CN, Wentzel-Larsen T, Lund-Johansen M. Conservative management of vestibular schwannoma - A prospective cohort study: growth rates, models and predictors. Journal of Neurosurgery 116(4): 706-712, April 2012. Full text not available in BORA due to publisher restrictions. The article is available at: http://dx.doi.org/10.3171/2011.12.JNS111662Paper III: Breivik CN, Varughese JK, Wentzel-Larsen T, Vassbotn F, Lund-Johansen M. Conservative management of vestibular schwannoma - A prospective cohort study: Treatment, Symptoms and Quality of Life. Neurosurgery 70(5) :1072-1080, May 2012. Full text not available in BORA due to publisher restrictions. The article is available at: http://dx.doi.org/10.1227/NEU.0b013e31823f5afaPaper IV: Varughese JK, Wentzel-Larsen T, Pedersen PH, Mahesparan R, Lund-Johansen M. Gamma knife treatment of growing vestibular schwannoma in Norway: tumor control and predictors – a prospective study. Full text not available in BORA.
PublisherThe University of Bergen
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