Longitudinal Radiographic Outcomes of Vestibular Schwannoma in Single and Fractionated Stereotactic Radiosurgery: A Retrospective Cohort Study.

Management of vestibular schwannoma (VS) includes stereotactic radiosurgery (SRS) in single or fractionated treatments. There is a paucity of literature on the three-dimensional (3D) volumetric kinetics and radiological changes following SRS and no consensus on appropriate post-SRS surveillance imaging timeline. This is a retrospective cohort study with institutional review board approval. A total of 55 patients met study criteria. We collected volumetric kinetic data in VS treated with SRS over time using a target volume contouring software. We also tracked radiographic phenomena such as pseudoprogression and necrosis. A secondary objective was to describe our overall treatment success rate and any failures. For all treatments groups, pseudoprogression most typically occurred within 12 months post-SRS, after which tumor volumes on average normalized and then decreased from pretreatment size at the last follow-up. Only two patients required salvage therapy post-SRS and were considered SRS treatment failures. Both patients were in the five-fraction cohort but with a lower biologically equivalent dose. Our study is first to collect 3D volumetric kinetics of VS following single and fractionated SRS in contrast to extrapolations from single and two-dimensional measurements. Our longitudinal data also show initial increases in volume in the first 12 months post-SRS followed by later declines, setting up interesting questions regarding the utility of early posttreatment surveillance imaging in the asymptomatic patient. Finally, we show low rates of treatment failure (3.6%) and show in our cohort that SRS dose de-escalation posed a risk of treatment failure.

Current Volumetric Models Overestimate Vestibular Schwannoma Size Following Stereotactic Radiosurgery.

OBJECTIVE: Accurate volume assessment is essential for the management of vestibular schwannoma after stereotactic radiosurgery (SRS). A cuboidal approximation for volume is the standard surveillance method; however, this may overestimate tumor volume. We sought to evaluate several volumetric models and their suitability for post-SRS surveillance. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: We evaluated 54 patients with vestibular schwannoma before and after SRS. INTERVENTION(S): Gold-standard volumes were obtained by a radiation oncologist using contouring software. Volume was also calculated by cuboidal, ellipsoidal, and spherical formulae using tumor diameters obtained by a neuroradiologist. MAIN OUTCOME MEASURE(S): Percent error (PE) and absolute percent error (APE) were calculated. Paired t test evaluated bias, and the Bland-Altman method evaluated reproducibility. Linear regression evaluated predictors of model error. RESULTS: All models overestimated volume compared with the gold standard. The cuboidal model was not reproducible before SRS (p < 0.001), and no model was reproducible after SRS (cuboidal p < 0.001; ellipsoidal p = 0.02; spherical p = 0.02). Significant bias was present before SRS for the cuboidal model (p < 0.001), and post-SRS for all models [cuboidal (p < 0.001), ellipsoidal (p < 0.02), and spherical (p = 0.005)]. Model error was negatively associated with pretreatment volume for the cuboidal (PE p = 0.03; APE p = 0.03), ellipsoidal (PE p = 0.03; APE p = 0.04), and spherical (PE p = 0.02; APE p = 0.03) methods and lost linearity post-SRS. CONCLUSIONS: The standard cuboidal practice for following vestibular schwannoma tumor volume after SRS overestimates size. Ellipsoidal and spherical estimations have improved performance but also overestimate volume and lack reliability post-SRS. The development of other volumetric models or application of contouring software should be investigated.

A Retrospective Cohort Study of Longitudinal Audiologic Assessment in Single and Fractionated Stereotactic Radiosurgery for Vestibular Schwannoma.

BACKGROUND: Fractionated stereotactic radiosurgery (SRS) for vestibular schwannomas (VS) has been theorized to allow for tumor control with higher rates of hearing preservation in selected patients with useful hearing. However, there is a paucity of literature with formal audiologic measures of hearing preservation to support the standard use of fractionated SRS in VS. We hypothesized that fractionation would diminish the amount of hearing damage. OBJECTIVE: To evaluate the relationship between audiologic performance and SRS fractionation scheme. METHODS: We performed an IRB-approved retrospective review of patients treated with 1, 3, or 5 fraction SRS for VS at our institution from 1998 to 2016. Pre- and post-SRS audiograms with speech awareness threshold (SAT) in treated and contralateral ears were obtained. Contralateral ear measurements were used for hearing normalization to account for presbycusis. RESULTS: Fifty-six patients with median audiologic follow-up 2.0 yr (mean 2.66 yr, min-max 0.50-9.45 yr) were included. Patients treated with single fractionation had a significantly worsened SAT (dB) compared to patients treated with 5 fractions (P = .008) and compared to all multifraction patients (P = .009) at 12 to 24 mo follow-up. CONCLUSION: This retrospective analysis supports the use of fractionated SRS to preserve hearing in patients with VS. SAT can be used as an objective metric of hearing response to radiosurgery.

Impairment of memory generalization in preclinical autosomal dominant Alzheimer's disease mutation carriers.

Fast, inexpensive, and noninvasive identification of Alzheimer's disease (AD) before clinical symptoms emerge would augment our ability to intervene early in the disease. Individuals with fully penetrant genetic mutations causing autosomal dominant Alzheimer's disease (ADAD) are essentially certain to develop the disease, providing a unique opportunity to examine biomarkers during the preclinical stage. Using a generalization task that has previously shown to be sensitive to medial temporal lobe pathology, we compared preclinical individuals carrying ADAD mutations to noncarrying kin to determine whether generalization (the ability to transfer previous learning to novel but familiar recombinations) is vulnerable early, before overt cognitive decline. As predicted, results revealed that preclinical ADAD mutation carriers made significantly more errors during generalization than noncarrying kin, despite no differences between groups during learning or retention. This impairment correlated with the left hippocampal volume, particularly in mutation carriers. Such identification of generalization deficits in early ADAD may provide an easily implementable and potentially linguistically and culturally neutral way to identify and track cognition in ADAD.