Predictive Value of Ki-67 Index in Evaluating Sporadic Vestibular Schwannoma Recurrence: Systematic Review and Meta-analysis

Abstract

Background: Ki-67 is often used as a proliferation index to evaluate how aggressive a tumor is and its likelihood of recurrence. Vestibular schwannomas (VS) are a unique benign pathology that lends itself well to evaluation with Ki-67 as a potential marker for disease recurrence or progression following surgical resection. Methods: All English language studies of VSs and Ki-67 indices were screened. Studies were considered eligible for inclusion if they reported series of VSs undergoing primary resection without prior irradiation, with outcomes including both recurrence/progression and Ki-67 for individual patients. For published studies reporting pooled Ki-67 index data without detailed by-patient values, we contacted the authors to request data sharing for the current meta-analysis. Studies reporting a relationship between Ki-67 index and clinical outcomes in VS for which detailed patients’ outcomes or Ki-67 indices could not be obtained were incorporated into the descriptive analysis, but excluded from the formal (i.e., quantitative) meta-analysis. Results: A systematic review identified 104 candidate citations, of which 12 met inclusion criteria. Six of these studies had accessible patient-specific data. Individual patient data were collected from these studies for calculation of discrete study effect sizes, pooling via random-effects modeling with restricted maximum likelihood, and meta-analysis. The standardized mean difference in Ki-67 indices between those with and without recurrence was calculated as 0.79% (95%CI=0.28-1.30; P=0.0026). Conclusion: Ki-67 index may be higher in VSs that demonstrate recurrence/progression following surgical resection. This may represent a promising means of evaluating tumor recurrence and potential need for early adjuvant therapy for VSs.