Biologically effective dose correlates with linear tumor volume changes after upfront single-fraction stereotactic radiosurgery for vestibular schwannomas

Abstract

Vestibular schwannomas (VSs) are benign, slow-growing tumors. Management options include observation, surgery, and radiation. In this retrospective trial, we aimed at evaluating whether biologically effective dose (BED) plays a role in tumor volume changes after single-fraction first intention stereotactic radiosurgery (SRS) for VS. We compiled a single-institution experience (n = 159, Lausanne University Hospital, Switzerland). The indication for SRS was decided after multidisciplinary discussion. Only cases with minimum 3 years follow-up were included. The Koos grading, a reliable method for tumor classification was used. Radiosurgery was performed using Gamma Knife (GK) and a uniform marginal prescription dose of 12 Gy. Mean BED was 66.3 Gy (standard deviation 3.8, range 54.1-73.9). The mean follow-up period was 5.1 years (standard deviation 1.7, range 3-9.2). The primary outcome was changes in 3D volumes after SRS as function of BED and of integral dose received by the VS. Random-effect linear regression model showed that tumor volume significantly and linearly decreased over time with higher BED (p < 0.0001). Changes in tumor volume were also significantly associated with age, sex, number of isocenters, gradient index, and Koos grade. However, the effect of BED on tumor volume change was moderated by time after SRS and Koos grade. Lower integral doses received by the VSs were inversely correlated with BED in relationship with tumor volume changes (p < 0.0001). Six (3.4%) patients needed further intervention. For patients having uniformly received the same marginal dose prescription, higher BED linearly and significantly correlated with tumor volume changes after SRS for VSs. BED could represent a potential new treatment paradigm for patients with benign tumors, such as VSs, for attaining a desired radiobiological effect. This could further increase the efficacy and decrease the toxicity of SRS not only in benign tumors but also in other SRS indications.

Keywords: Biologically effective dose; Gamma Knife; Radiosurgery; Tumor; Vestibular schwannoma; Volume.

Fig. 1

The therapeutic tumor volumes were not normally distributed (Fig. 1a); in this respect, a logarithmic transformation was done (Fig. 1b ); the mean tumor volume at the time of SRS receiving the radiation dose and during follow-up course (c for each individual patient and d for all patients, censored at 7 years)

Fig. 2

Volume decrease during follow-up course at 3, 5, and 7 years after single-fraction SRS and function of BED

Fig. 3

Volumetric decrease during follow-up course at 3, 5, and 7 years after single-fraction SRS is more important for BED in 1st, 2nd, and 3rd quartiles

Fig. 4

From left to right, correlations between VSs’ volumes (from up to down at baseline, 3, 5, and >  = 7 years) and BED (left), integral dose received by the tumor volume (right) (p < 0.0001)