OBJECTIVE The aim of this study was to gain insight into the influence of the pretreatment growth rate on the volumetric tumor response and tumor control rates after Gamma Knife radiosurgery (GKRS) for incidental vestibular schwannoma (VS). METHODS All patients treated with GKRS at the Gamma Knife Center, ETZ Hospital, who exhibited a confirmed radiological progression of their VS after an initial observation period were included. Pre- and posttreatment MRI scans were volumetrically evaluated, and the volume doubling times (VDTs) prior to treatment were calculated. Posttreatment volumes were used to create an objective mathematical failure definition: 2 consecutive significant increases in tumor volume among 3 consecutive follow-up MRI scans. Spearman correlation, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis were used to determine the influence of the VDT on the volumetric treatment response. RESULTS The resulting patient cohort contained 311 patients in whom the VDT was calculated. This cohort had a median follow-up time of 60 months after GKRS. Of these 311 patients, 35 experienced loss of tumor control after GKRS. The pretreatment growth rate and the relative volume changes, calculated at 6 months and 1, 2, and 3 years following treatment, showed no statistically significant correlation. Kaplan-Meier analysis revealed that slow-growing tumors, with a VDT equal to or longer than the median VDT of 15 months, had calculated 5- and 10-year control rates of 97.3% and 86.0%, respectively, whereas fast-growing tumors, with a VDT less than the median growth rate, had control rates of 85.5% and 67.6%, respectively (log-rank, p = 0.001). The influence of the VDT on tumor control was also determined by employing the Cox regression analysis. The resulting model presented a significant (p = 0.045) effect of the VDT on the hazard rates of loss of tumor control. CONCLUSIONS By employing a unique, large database with long follow-up times, the authors were able to accurately investigate the influence of the pretreatment VS growth rate on the volumetric GKRS treatment response. The authors have found a predictive model that illustrates the negative influence of the pretreatment VS growth rate on the efficacy of radiosurgery treatment. The resulting tumor control rates confirm the high efficacy of GKRS for slow-growing VS. However, fastgrowing tumors showed significantly lower control rates. For these cases, different treatment strategies may be considered.

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Keywords acoustic neuroma, Gamma Knife radiosurgery, pretreatment growth rate, treatment failure definition, vestibular schwannoma, volumetric tumor response, stereotactic radiosurgery
Persistent URL dx.doi.org/10.3171/2018.6.Jns18516, hdl.handle.net/1765/122326
Journal Journal of Neurosurgery
Langenhuizen, P., Zinger, S, Hanssens, P.E., Kunst, HPM, Mulder, JJS, Leenstra, S, … Verheul, JB. (2019). Influence of pretreatment growth rate on Gamma Knife treatment response for vestibular schwannoma: a volumetric analysis. Journal of Neurosurgery, 131(5), 1405–1412. doi:10.3171/2018.6.Jns18516