Predictive Factors of Pseudoprogression in Vestibular Schwannoma Treated with Fractionated Stereotactic Radiotherapy

Objective: Fractionated stereotactic radiotherapy (FSRT) is a well-established treatment for vestibular schwannoma (VS). Tumour pseudoprogression may lead to worsening symptoms leading to the necessity of urgent salvage surgery. This study aimed to assess the predictive factors of pseudoprogression and treatment related toxicities in VS treated with FSRT. Methods: This retrospective cohort study included all patients with VS treated with FSRT between 1999 and 2015. Risk factors assessed included sex, age, previous surgical resection, tumour diameter, gross tumour volume, planning target volume, overall treatment time, equivalent dose in 2-Gy fractions, and the presence of brainstem or cerebellar compression prior to radiotherapy. Fisher's exact test and two-sample t test were used for statistical analysis. Results: Eighteen patients were included. The median follow-up time was 80.3 months. The overall disease control rate after FSRT was 94.4%. Of the 18 patients, one (5.6%) developed local tumour progression, seven (38.9%) underwent tumour pseudoprogression; and 10 (55.6%) had stable disease. Median time to tumour pseudoprogression was 8.63 months (range, 4.5-13.1 months). Tumours with pseudoprogression and those with at least stable disease had a mean diameter of 2.7 cm and 2.1 cm, respectively (p = 0.18). The mean treatment planning target volume in the pseudoprogression group was larger than that in the non-progression group with volume measured (22.2 cc vs. 10.0 cc; p = 0.04). Patients with brainstem or cerebellar compression observed on magnetic resonance imaging before radiotherapy were associated with a higher risk of pseudoprogression (p = 0.0498). The overall salvage surgery rate was 17.7%. Conclusion: Upfront surgery may be more desirable than FSRT for those surgically fit patients with considerable treatment volume and evidence of mass effect. Large prospective studies are needed to confirm our findings and to identify further predictive factors for pseudoprogression.