Aspirin Intake Correlates With Halted Growth of Sporadic Vestibular Schwannoma In Vivo

Kandathil, Cherian K.; Dilwali, Sonam; Wu, Chen‐Chi; İbrahimov, Metin; McKenna, Michael J.; Lee, Hang; Stanković, Konstantina M.

doi:10.1097/mao.0000000000000189

Cited by 43 publications

(51 citation statements)

References 19 publications

(20 reference statements)

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“…Not only do our results reinforce previously documented relationships between the maximum tumor diameter at presentation and disequilibrium with tumor growth, but lack of association between patient age(9,19,22,27), gender(9,19,27), hearing loss(9,27) and tinnitus(25) corroborate results from previously smaller studies. Nonetheless, our findings contradict a few previously reported statistically significant associations with VS growth; these include tinnitus(9,22) and aspirin use(28). While there may truly be no association between tumor growth and tinnitus or aspirin use, sampling error, growth definitions, and recall bias, among other issues, could account for the discrepancy between our results and previous findings.…”

Section: Discussioncontrasting

confidence: 99%

Single Institutional Experience With Observing 564 Vestibular Schwannomas

Hunter

Francis

O’Connell

et al. 2016

Otology &Amp; Neurotology

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Objective To characterize the risk and predictors of growth during observation of vestibular schwannomas (VS). Study Design Retrospective case series. Setting Single academic, tertiary care center. Patients 564 consecutive VS patients who underwent at least two MRI studies prior to intervention. Intervention(s) Serial MRI studies Main outcome measure(s) Tumor growth, defined as a ≥2 mm increase in the maximum tumor diameter between consecutive MRI studies, or between the first and last study. Results A total of 1,296 patients (1995–2015) with VS were identified. Of those, 564 patients (median age 59.2 years; 53.5% female) were initially observed and underwent multiple MRI studies (median follow-up 22.9 months, interquartile range [IQR] 11.7 – 42.7). The median maximum tumor diameter at presentation was 1.00 cm (IQR 0.6 – 1.51 cm). In all, 40.8% of tumors demonstrated growth and 32.1% underwent intervention (21.5% microsurgery, 10.5% radiation) during the surveillance period. Multivariable Cox regression analysis showed that for each tumor, the risk of growth or intervention was significantly increased for larger initial VS diameters (HR=2.22; 95% CI: 1.90 – 2.61) and when disequilibrium was a presenting symptom (HR=1.70; 95% CI: 1.30 – 2.23). Patient age, gender, aspirin use and presenting symptoms of asymmetric hearing loss, tinnitus, and vertigo, were not associated with tumor growth. Conclusions To date, this is the largest series of observed VS reported in the literature. Risk of VS growth is significantly increased among patients who present with larger tumors and who have concomitant disequilibrium. IRB 151481 Define Professional Practice Gap & Educational Need No cohort with this sample size has assessed vestibular schwannoma growth rates in conjunction with this number of variables. Learning Objective To characterize vestibular schwannoma growth rates and predictors of growth.

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Section: Discussioncontrasting

confidence: 99%

Single Institutional Experience With Observing 564 Vestibular Schwannomas

Hunter

Francis

O’Connell

et al. 2016

Otology &Amp; Neurotology

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“…We found clinically well-tolerated COX-2 inhibitors, namely aspirin, NaSal and 5-ASA, to minimize proliferation of VS cells, without affecting healthy SCs. Our in vitro findings corroborate our retrospective clinical observation that the probability of VS growth decreased to approximately half in patients taking aspirin (20). To the best of our knowledge, salicylates would be the most promising treatments against sporadic VS as they are commonly used for other pathologies, including other tumors such as colon cancer, with minimal side effects when utilized within the clinically well-established therapeutic range.…”

Section: Discussionsupporting

confidence: 89%

“…Our in vitro results parallel our findings of a clinical study in which we correlated the growth rates of human VSs, calculated by measuring changes in tumor size on serial MRI scans, with the patient's intake of aspirin (for unrelated medical diagnoses to VS) (20). In that retrospective study, based on a review of the medical records over the last 32 years at our clinical center, we found that the probability of VS growth in patients who took aspirin was approximately half of that in VS patients who did not take aspirin (20). Medical records that specified aspirin dose reported oral intake of either 81 mg or 325 mg daily, with most (38) patients taking 81 mg for co-morbidities such as cardiovascular disease.…”

Section: Discussionsupporting

confidence: 79%

Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas

Dilwali

Kao

Fujita

et al. 2015

Translational Research

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Vestibular schwannomas (VSs) are the most common tumors of the cerebellopontine angle. Significant clinical need exists for pharmacotherapies against VSs. Motivated by previous findings that immunohistochemical expression of cyclooxygenase 2 (COX-2) correlates with VS growth rate, we investigated the role of COX-2 in VSs and tested COX-2 inhibiting salicylates against VSs. COX-2 was found to be aberrantly expressed in human VS and primary human VS cells in comparison to control human nerve specimens and primary Schwann cells (SCs), respectively. Further, levels of prostaglandin E2, the downstream enzymatic product of COX-2, correlated with primary VS culture proliferation rate. Because COX-2 inhibiting salicylates such as aspirin are well-tolerated and frequently clinically used, we assessed their repurposing for VS. Changes in proliferation, cell death and cell viability were analyzed in primary VS cultures treated with aspirin, sodium salicylate (NaSal) or 5-aminosalicylic acid (5-ASA). These drugs did not increase VS cell death nor affect healthy SCs. The cytostatic effect of aspirin in vitro was in concurrence with our previous clinical finding that VS patients taking aspirin demonstrate reduced tumor growth. Overall, this work suggests that COX-2 is a key modulator in VS cell proliferation and survival, and highlights salicylates as promising pharmacotherapies against VS.

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“…Traditionally, there is a known association of MPNST and NF1 (59,61). These patients already have a germ line loss of one tumor suppressor gene.…”

Section: Discussionmentioning

confidence: 98%

Evaluation of Reported Malignant Transformation of Vestibular Schwannoma

Maducdoc¹,

Ghavami²,

Linskey³

et al. 2015

Otology &Amp; Neurotology

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The potential mechanism leading to malignant transformation of VS seems more obvious for SRS and is less understood for MS. Given a low incidence of de novo malignant schwannoma, the possibility that these are spontaneous events in either setting cannot be ruled out. Risk of malignant transformation of VS after either SRS or MS is not zero; however, the magnitude of this risk is probably minimal based on the evidence from eight histopathologically confirmed cases.

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Aspirin Intake Correlates With Halted Growth of Sporadic Vestibular Schwannoma In Vivo

Abstract: Our results suggest a potential therapeutic role of aspirin in inhibiting sVS growth.

Cited by 43 publications

References 19 publications

Single Institutional Experience With Observing 564 Vestibular Schwannomas

Single Institutional Experience With Observing 564 Vestibular Schwannomas

Nonsteroidal anti-inflammatory medications are cytostatic against human vestibular schwannomas

Evaluation of Reported Malignant Transformation of Vestibular Schwannoma

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