Age, preoperative tumor volume and widening of the internal acoustic meatus are independent factors associated with poor preoperative hearing in vestibular schwannoma patients - results of a single-center retrospective analysis.

Preoperative hearing function shows wide variations among patients diagnosed with vestibular schwannoma. Besides the preoperative tumor size there are other factors that influence the preoperative hearing function that are frequently discussed. A comprehensive analysis of a large cohort of vestibular schwannomas has the potential to describe new insights and influence the preoperative management. We analyzed clinical factors, imaging data and the expression of the proliferation marker MIB1 as potential influencing factors on the preoperative hearing function in a retrospective cohort of 523 primary sporadic vestibular schwannomas. The results of the preoperative audiometry were quantified using the Gardner-Robertson Score. Uni- and multivariate analyses were performed. Serviceable hearing (Gardner-Robertson class 1 or 2) was documented in 391 patients (74.8%). Factors associated with non-serviceable hearing (Gardner-Robertson class 3-5) were patients of older age (p < 0.0001), larger preoperative tumor volume (p = 0.0013) and widening of the internal acoustic meatus compared to the healthy side (p = 0.0353). Gender and differences in the expression of the proliferation marker MIB1 had no influence on preoperative hearing. In the multivariate nominal logistic regression older age (OR 27.60 (CI 9.17-87.18), p < 0.0001), larger preoperative tumor volume (OR 20.20 (CI 3.43-128.58), p = 0.0011) and widening of the internal acoustic canal (OR 7.86 (CI 1.77-35.46), p = 0.0079) remained independent factors associated with non-serviceable hearing. Widening of the internal acoustic canal is an independent factor for non-serviceable preoperative hearing in vestibular schwannoma patients together with older age and larger preoperative tumor volume.

Correction: Gonçalves et al. Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort. Cancers 2021, 13, 466.

The authors would like to make a correction to their published paper [...].

COX2 expression is associated with preoperative tumor volume but not with volumetric tumor growth in vestibular schwannoma.

OBJECTIVE: Vestibular schwannomas (VS) are benign slow growing tumors arising from the vestibular nerve. The role of cyclooxygenase 2 (COX2) in tumor development of growth has been addressed in a few studies with contradictory results and suggestions. We recently analyzed the immunohistochemical expression of COX2 in 1044 VS samples and described an association of higher COX2 expression with proliferation but found no influence by regular intake of acetylsalicylic acid. We now collected volumetric radiographic data of the preoperative tumor volume and growth to further test the role of COX2 in VS growth. METHODS: Preoperative images of 898 primary sporadic vestibular schwannomas were assessed, and sufficient preoperative imaging was used for the volumetric measurement preoperative tumor volume (n = 747) and preoperative relative tumor growth (n = 171). Clinical parameters and results of the immunohistochemical expression of COX2 and MIB1 in resected tumor tissue samples were obtained from our prior study. ANOVA, CART-analysis and multivariate nominal logistic regression were used for statistical analysis. RESULTS: Larger preoperative tumor volumes were observed with tumors of younger patients (p = 0.0288) and with higher COX2 expression scores (p < 0.0001). Higher MIB1 expression was associated with smaller tumors (p = 0.0149) but with increased radiographic tumor growth (p = 0.0003). Patients of older age had tumors with slower growth rates (p = 0.0311). In the multivariate analysis only MIB1 expression was an independent significant factor regarding tumor growth (p = 0.0002). CONCLUSIONS: Higher expression of COX2 in schwannoma is associated with an increased preoperative tumor volume but not with radiographic tumor growth over time.

Macrophage and Lymphocyte Infiltration Is Associated with Volumetric Tumor Size but Not with Volumetric Growth in the Tübingen Schwannoma Cohort.

Most patients with vestibular schwannomas can be cured with microsurgical resection, or tumor growth can be stabilized by radiotherapy in certain cases. Recurrence is rare but usually difficult to treat. Treatment alternatives to local therapies are not established. There is growing evidence of the role of inflammatory processes in schwannomas, which may be exploitable by targeted innovative therapies. To further define the impact of inflammation with tumor growth in vestibular schwannoma, we performed immunohistochemical analyses of CD3, CD8, CD68 and CD163 to assess lymphocyte and macrophage infiltration in 923 tumor tissue samples of surgically resected vestibular schwannomas. An inflammatory score was compared with tumor size and volumetric growth. We observed a significantly larger preoperative tumor size with increased expression rates of CD3, CD8, CD68 and CD163 (p < 0.0001, p < 0.0001, p = 0.0015 and p < 0.0001, respectively), but no differences in percentual volumetric tumor growth. When all four markers were combined as an inflammatory score, tumors with high inflammatory infiltration showed slower percentual growth in a multivariate analysis, including MIB1 expression (p = 0.0249). We conclude that inflammatory cell infiltration increases with larger tumor size but is associated with slower percentual volumetric tumor growth.

COX2 expression is associated with proliferation and tumor extension in vestibular schwannoma but is not influenced by acetylsalicylic acid intake.

Acetylsalicylic acid has been linked to a lower risk for different cancer types, presumably through its inhibitory effect on cyclooxygenase 2. This has also been investigated in vestibular schwannomas with promising results suggesting an antiproliferative effect and recently the intake has been recommended for vestibular schwannomas as a conservative treatment option. We constructed tissue microarrays from paraffin-embedded tissue samples of 1048 vestibular schwannomas and analyzed the expression of cyclooxygenase 2 and the proliferation marker MIB1 (Molecular Immunology Borstel) via immunohistochemistry together with clinical data (age, gender, tumor extension, prior radiotherapy, neurofibromatosis type 2, tumor recurrence, cyclooxygenase 2 responsive medication). Univariate analysis showed that cyclooxygenase 2 expression was increased with age, female gender, prior radiotherapy and larger tumor extension. MIB1 expression was also associated with higher cyclooxygenase 2 expression. Schwannomas of neurofibromatosis type 2 patients had lower cyclooxygenase 2 levels. Use of acetylsalicylic acid, non-steroidal anti-inflammatory drugs, glucocorticoids or other immunosuppressants did not show differences in cyclooxygenase 2 or MIB1 expression. Instead, cyclooxygenase 2 expression increases with tumor extension while MIB1 expression is not associated with tumor size. Overall, cyclooxygenase 2 expression is associated with proliferation but not influenced by regular intake of acetylsalicylic acid or other cyclooxygenase 2-responsive medications. Acetylsalicylic acid intake does not alter cyclooxygenase 2 expression and has no antiproliferative effect in vestibular.