Aspirin does not prevent growth of vestibular schwannomas: A case‐control study

MacKeith, Samuel; Wasson, Joseph; Baker, Charlotte; Guilfoyle, Matthew; John, Deepa; Donnelly, Neil; Mannion, Richard; Jefferies, Sarah; Axon, Patrick; Tysome, James R.

doi:10.1002/lary.27114

Cited by 16 publications

(19 citation statements)

References 40 publications

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“…The correlation between the PET assessment and inflammatory cell density was preserved and so this did not detract from the potential of 11 C-( R )-PK11195 as a biomarker, but the reason for high immunohistochemical TSPO labeling in this case could not be clarified. Previous studies have shown that tumor size itself is a predictive marker of VS growth, 49 although this is not universally accepted. Separating the relative contributions of tumor size and growth rate to 11 C-( R )-PK11195 specific binding from our data is difficult as the growing tumors were also statistically significantly larger.…”

Section: Discussionmentioning

confidence: 99%

Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma

et al. 2018

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BackgroundInflammation is hypothesized to be a key event in the growth of sporadic vestibular schwannoma (VS). In this study we sought to investigate the relationship between inflammation and tumor growth in vivo using the PET tracer 11C-(R)-PK11195 and dynamic contrast enhanced (DCE) MRI derived vascular biomarkers.MethodsNineteen patients with sporadic VS (8 static, 7 growing, and 4 shrinking tumors) underwent prospective imaging with dynamic 11C-(R)-PK11195 PET and a comprehensive MR protocol, including high temporal resolution DCE-MRI in 15 patients. An intertumor comparison of 11C-(R)-PK11195 binding potential (BPND) and DCE-MRI derived vascular biomarkers (Ktrans, vp, ve) across the 3 different tumor growth cohorts was undertaken. Tissue of 8 tumors was examined with immunohistochemistry markers for inflammation (Iba1), neoplastic cells (S-100 protein), vessels (CD31), the PK11195 target translocator protein (TSPO), fibrinogen for vascular permeability, and proliferation (Ki-67). Results were correlated with PET and DCE-MRI data.ResultsCompared with static tumors, growing VS displayed significantly higher mean 11C-(R)-PK11195 BPND (−0.07 vs 0.47, P = 0.020), and higher mean tumor Ktrans (0.06 vs 0.14, P = 0.004). Immunohistochemistry confirmed the imaging findings and demonstrated that TSPO is predominantly expressed in macrophages. Within growing VS, macrophages rather than tumor cells accounted for the majority of proliferating cells.ConclusionWe present the first in vivo imaging evidence of increased inflammation within growing sporadic VS. Our results demonstrate that 11C-(R)-PK11195 specific binding and DCE-MRI derived parameters can be used as imaging biomarkers of inflammation and vascular permeability in this tumor group.

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Section: Discussionmentioning

confidence: 99%

Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma

et al. 2018

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“…On the contrary Hunter et al showed no effect of ASA intake on tumor growth in a series of 564 VS [13]. A most recent study assessed 437 cases and found no impact on ASA as well [21]. The Congress of Neurological Surgeons recently recommended the administration of aspirin for patients with vestibular schwannomas as an antiproliferative treatment [32].…”

Section: Discussionmentioning

confidence: 99%

“…In this cohort there was no association between tumor extension and MIB1 expression. Suggestions have been made that the current tumor size is a factor influencing future tumor growth [21]. However, in the study by MacKeith and colleagues, growth was defined as 2 mm increase in diameter, which does not represent the true percentual increase of the tumor volume and is obsolete for tumor volume and growth assessment [21, 31].…”

Section: Discussionmentioning

confidence: 99%

“…Later, Dilwali et al were able to show that the application of acetylsalicylic acid (ASA) decreases COX2 expression and cell growth in vitro, an effect not observed in a normal schwann cell culture [7]. Three retrospective analyses presented conflicting results regarding the antiproliferative effect of ASA intake in sporadic VS. Kandathil et al demonstrated a correlation of ASA intake and decreased tumor growth [17, 18] while no efficacy was observed in two other cohort studies of similar sample size [13, 21]. A prospective phase II, randomized, double-blind longitudinal study is currently recruiting patients with vestibular schwannomas to investigate the effect of ASA on tumor growth and hearing preservation (NCT03079999).…”

Section: Introductionmentioning

confidence: 99%

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

Behling

Ries

Skardelly

et al. 2019

acta neuropathol commun

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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.

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“…They found a significant inverse association with aspirin users and tumour growth (OR 0.32, 95% CI 0.11-0.91) [82]. Although two similar retrospective analyses did not find an inverse association, they did not observe increased tumour growth with aspirin or other NSAID users [83,84]. Therefore, a level 3 recommendation exists in the CNS stating aspirin may be considered for patients undergoing observation [73].…”

Section: Emerging Treatmentsmentioning

confidence: 96%

Vestibular Schwannoma: What We Know and Where We are Heading

Gupta

Thakker

Gupta

2020

Head and Neck Pathol

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Vestibular schwannoma (VS) is a Schwann cell-derived tumour arising from the vestibulocochlear nerve. Although benign, it represents a threat to intracranial structures due to mass effect and carries a small risk of malignant transformation. VS therefore represents an important healthcare burden. We review the literature regarding pathogenesis, risk factors, and diagnosis of VS. The current and future potential management strategies are also discussed. A narrative review of all relevant papers known to the authors was conducted. The majority of VS remain clinically stable and do not require interventional procedures. Nevertheless, various surgical techniques exist for removing VS, the most common of which are translabyrinthine and retrosigmoid approaches. Due to surgical risks such as hearing loss, facial nerve dysfunction, post-operative headache, and cerebrospinal fluid leakage, a "watch and rescan" approach is adopted for most patients. Radiotherapy is a useful alternative and has been shown to have a similar response for growth restriction. Due to the heterogeneous nature of VS, there is a lack of consensus regarding management of tumours that are too large for conservative management but too small to indicate surgery. Emerging biologic therapies, such as Bevacizumab, Everolimus, and Lapatinib, as well as antiinflammatories like aspirin are promising potential treatments; however, long-term evidence of their efficacy is required. The knowledge base regarding VS continues to improve. With increased understanding of the pathogenesis of these tumors, we believe future work should focus on pharmacologic intervention. Biologic therapies aimed toward improved patient outcomes are particularly promising.

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Aspirin does not prevent growth of vestibular schwannomas: A case‐control study

Abstract: 3b. Laryngoscope, 128:2139-2144, 2018.

Cited by 16 publications

References 40 publications

Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma

Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma

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

Vestibular Schwannoma: What We Know and Where We are Heading

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