Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma

Graffeo, Christopher S.; Perry, Avital; Raghunathan, Aditya; Jentoft, Mark E.; Driscoll, Colin L. W.; Neff, Brian A.; Carlson, Matthew L.; Jacob, Jeffrey T.; Link, Michael; Gompel, Jamie Van

doi:10.1055/s-0037-1600614

Cited by 4 publications

(10 citation statements)

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Section: Discussionmentioning

confidence: 99%

“…Although the composition varies with each tumor, immune cells can infiltrate the TME and take on several roles that promote and/or resist inflammation and tumor proliferation. 24 Although the mechanisms have not been fully elucidated, several studies have found associations between TAMs, tumor growth, and HL in VS. 5,22,[25][26][27][28] In a retrospective investigation of 46 patients with VS with subtotal resections, Graffeo et al 25 found that higher macrophage density (defined as the ratio of CD68 1 macrophages to S100 1 cells) was significantly associated with tumor progression postoperatively. However, it was unknown whether M1 and/or M2 macrophages were implicated, as CD68 is a nonspecific pan-macrophage marker.…”

Section: Discussionmentioning

confidence: 99%

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Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

et al. 2021

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Objective (1) Characterize the distribution of M1 and M2 macrophages in vestibular schwannomas by hearing status. (2) Develop assays to assess monocyte migration and macrophage polarization in cocultures with vestibular schwannoma cells. Study Design Basic and translational science. Setting Tertiary care center. Methods A retrospective chart review of 30 patients with vestibular schwannoma (VS) was performed. Patients were stratified into serviceable and unserviceable hearing groups. Immunohistochemistry for CD80+ M1 and CD163+ M2 macrophages was conducted. Primary VS cultures (n = 4) were developed and cocultured with monocytes. Immunohistochemistry for macrophage markers was performed to assess monocyte migration and macrophage polarization. Results Although tumors associated with unserviceable hearing had higher levels of CD80 and CD163 than those with serviceable hearing, the relationship was only significant with CD163 ( P = .0161). However, CD163 level did not remain a significant predictor variable associated with unserviceable hearing on multivariate analysis when adjusted for other variables. In vitro assays show that VS cells induced monocyte migration and polarization toward CD80+ M1 or CD163+ M2 macrophage phenotypes, with qualitative differences in CD163+ macrophage morphologies between serviceable and unserviceable hearing groups. Conclusion Vestibular schwannomas express varying degrees of CD80+ M1 and CD163+ M2 macrophages. We present evidence that higher expression of CD163+ may contribute to poorer hearing outcomes in patients with VS. We also describe in vitro assays in a proof-of-concept investigation that VS cells can initiate monocyte migration and macrophage polarization. Future investigations are warranted to explore the relationships between tumor, macrophages, secreted cytokines, and hearing outcomes in patients with VS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

et al. 2021

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“…A total of 12 studies were identified as reporting a specific analysis of K i -67 index as a predictor of clinical outcomes after resection for VS. 2 9 10 11 12 13 14 15 16 17 18 19 20 Among these studies, six specifically assessed the relationship between K i -67 index and tumor recurrence/progression, with five identifying a statistically significant relationship between increased K i -67 positivity and treatment failure. Another five studies studied a variety of primary endpoints in relation to K i -67 indices, including preoperative tumor size, preoperative tumor growth rate, and preoperative symptoms.…”

Section: Resultsmentioning

confidence: 99%

“…Principally, the K i -67 antigen and associated index calculations have been validated for several related disease processes—most importantly, meningioma—as well as across numerous institutions and patient populations that lend robustness to the generalization of its utility. 2 9 10 12 14 15 16 17 18 19 20 29 Additionally, phenotypically aggressive disease behavior has been associated with increased K i -67 staining in several other central nervous system neoplasms, such as dural infiltration and associated disease recurrence in pituitary adenomas. 30…”

Section: Discussionmentioning

confidence: 99%

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

Vakharia

Hasegawa²,

Graffeo

et al. 2022

J Neurol Surg B Skull Base

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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.

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“…The location of tumor remnant has also been implicated; residual tumor within the internal auditory canal (IAC) has been linked to postoperative tumor progression (12). Pathologic analyses of resected tumor specimens have proposed an association between remnant tumor progression and an upregulated immune reactivity as demonstrated by increased macrophage density and molecular immunology borstel (MIB-1) index (cell proliferation marker) (7,13,14).…”

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confidence: 99%

Predictors of Recurrence After Sub-total or Near-total Resection of Vestibular Schwannoma: Importance of Tumor Volume and Ventral Extension

Manzoor

Nassiri²,

Sherry³

et al. 2022

Otology &Amp; Neurotology

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Objective:To evaluate the predictors of remnant tumor regrowth and need for salvage therapy after less than gross total resection (GTR) of vestibular schwannoma (VS).Study Design:Retrospective chart review.Setting:Tertiary neurotologic referral center.Patients:Patients who underwent VS resection between 2008 and 2019 either with GTR, near total resection (NTR), and subtotal resection (STR).Interventions:Microsurgical resection, salvage radiosurgery.Main Outcome Measures:Regrowth free interval, salvage free interval, tumor doubling rate.Results:Three hundred eighty five cases (GTR = 236, NTR = 77, and STR = 71) from 2008 to 2019 were included. STR cohort had much larger and complex tumors with significant differences in tumor volume, ventral extension and brainstem compression (p < 0.001). On single predictor analysis, tumor volume, ventral extension, brainstem compression as well as STR strategy was associated with significant increased risk of regrowth and need for salvage therapy. Multivariate analysis revealed STR strategy as significant predictor of regrowth (hazard ratio 3.79, p < 0.0005). Absolute remnant volume and extent of resection (EOR) did not predict regrowth. A small proportion of cases (NTR = 4%, STR = 15%) eventually needed salvage radiosurgery with excellent ultimate local tumor control with no known recurrence to date.Conclusions:Conservative surgical strategy employing NTR or STR can be employed safely in large and complex VS. While there is increased risk of regrowth in the STR cohort, excellent local control can be achieved with appropriate use of salvage radiosurgery. No disceret radiologic or operative predictors of regrowth were identified.

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Macrophage Density Predicts Facial Nerve Outcome and Tumor Growth after Subtotal Resection of Vestibular Schwannoma

Cited by 4 publications

References 0 publications

Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

Tumor‐Associated Macrophages in Vestibular Schwannoma and Relationship to Hearing

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

Predictors of Recurrence After Sub-total or Near-total Resection of Vestibular Schwannoma: Importance of Tumor Volume and Ventral Extension

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