An update on the influence of the pretreatment growth rate on the efficacy of Gamma Knife radiosurgery for vestibular schwannomas

Introduction
Prognostic factors of tumor control after Gamma Knife radiosurgery (GKRS) for vestibular schwannomas (VS) remain largely unknown. Four years ago, we reported that the growth rate of VS before GKRS is indicative of the probability that radiosurgery achieves tumor control. These findings may have important implications for treatment strategies and may lead to advise for either microsurgery or higher marginal doses for fast-growing tumors. The objective of this study is to validate the previously obtained results in the correlation between the pretreatment growth rate and tumor control after GKRS, using an updated and significantly larger database.

Methods
Patients treated between 2002 and 2015 were identified, who had a pretreatment scan available of at least 6 months prior to treatment and had at least 2 years of follow-up after GKRS. Tumor volumes before, at, and after treatment were assessed. GKRS was performed in a uniform way with a marginal dose between 11 and 13 Gy. Treatment failure was defined as radiological progression beyond 2 years after GKRS. Volume doubling times (VDTs) before treatment were correlated with the observed tumor control rates and volumetric responses after treatment. Kaplan-Meier and Cox regression analyses were employed to investigate the effect of the VDT on the treatment response.

Results
A total of 402 patients met the inclusion criteria. The median follow-up time is 85 months. In this cohort, 50 patients showed a radiological failure. The resulting 5- and 10-year tumor control rates are 92.7% and 83.2%, respectively. The calculated VDTs vary between 3 and 344 months, with a median VDT of 15 months. Splitting the cohort into two sub-cohorts using the median VDT, results in 5- and 10-year control rates of 87.1% and 74.3% for the faster growing tumors, and 97.8% and 91.8% for the slower growing tumors, respectively (log-rank, p<0.001) (Figure 1). The Cox regression analyses demonstrate a statistically significant effect (p=0.009) of the pretreatment growth rate on tumor control, thereby enabling the probability calculation of obtaining tumor control after GKRS.

Conclusions
This updated and more extensive study clearly verifies our earlier findings: the pretreatment growth rate correlates with the observed tumor control after GKRS. More specifically, it denotes that fast-growing tumors are less likely to obtain tumor control. Our Cox regression model enables the calculation of the risk at treatment failure on an individual basis. Furthermore, these results might justify alterations in the management of VS.