Dataset Information

Elevated baseline C-reactive protein levels predict poor progression-free survival in sporadic vestibular schwannoma.

ABSTRACT:

Background

Recent investigations showed emerging evidence of the role of inflammation in the growth of sporadic vestibular schwannoma (VS). The present retrospective study investigated the impact of systemic inflammation on tumor progression using serum C-reactive protein (CRP) levels in a series of 87 surgically treated sporadic VS patients.

Methods

The optimal cut-off value for CRP was defined as 3.14 mg/dl according to the receiver operating characteristic curve (AUC: 0.70, 95% CI 0.47-0.92). Patient cohort was dichotomized into normal (n = 66; < 3.14 mg/dl) and high baseline (n = 21; ≥ 3.14 mg/dl) CRP groups.

Results

No significant differences in age, sex, comorbidities influencing the systemic inflammatory state, Karnofsky performance status (KPS), tumor size, extent of resection, or MIB-1 index were identified between the two groups defined by the baseline CRP levels. Univariable analysis demonstrated that a high CRP level (≥ 3.14 mg/dl) is significantly associated with a shortened progression-free survival (PFS) (hazard ratio (HR): 6.05, 95% CI 1.15-31.95, p = 0.03). Multivariable Cox regression analysis considering age, extent of resection, KPS, tumor size, and baseline CRP confirmed that an elevated CRP level (≥ 3.14 mg/dl) is an independent predictor of shortened PFS (HR: 7.20, 95% CI 1.08-48.14, p = 0.04).

Conclusions

The baseline CRP level thus serves as an independent predictor of PFS. Further investigations of the role of inflammation and tumor inflammatory microenvironment in the prediction of prognosis in sporadic VS are needed.

SUBMITTER: Wach J

PROVIDER: S-EPMC8816751 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Elevated baseline C-reactive protein levels predict poor progression-free survival in sporadic vestibular schwannoma.

Wach Johannes J Güresir Ági Á Borger Valeri V Schuss Patrick P Becker Albert A Coch Christoph C Schmitz Marie-Therese MT Hölzel Michael M Toma Marieta M Herrlinger Ulrich U Vatter Hartmut H Güresir Erdem E

Journal of neuro-oncology 20211209 2

<h4>Background</h4>Recent investigations showed emerging evidence of the role of inflammation in the growth of sporadic vestibular schwannoma (VS). The present retrospective study investigated the impact of systemic inflammation on tumor progression using serum C-reactive protein (CRP) levels in a series of 87 surgically treated sporadic VS patients.<h4>Methods</h4>The optimal cut-off value for CRP was defined as 3.14 mg/dl according to the receiver operating characteristic curve (AUC: 0.70, 95% ...[more]

PMID: 34882287

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Project description:Nearly two-thirds of patients with vestibular schwannoma (VS) are reporting a significantly impaired quality of life due to tinnitus. VS-associated tinnitus is attributed to an anatomical and physiological damage of the hearing nerve by displacing growth of the tumor. In contrast, the current pathophysiological concept of non-VS tinnitus hypothesizes a maladaptive neuroplasticity of the central nervous system to a (hidden) hearing impairment resulting in a subjective misperception. However, it is unclear whether this concept fits to VS-associated tinnitus. This study aims to determine the clinical predictors of VS-associated tinnitus to ascertain the compatibility of both pathophysiological concepts.This retrospective study includes a group of 478 neurosurgical patients with unilateral sporadic VS evaluated preoperatively regarding the occurrence of ipsilateral tinnitus depending on different clinical factors, i.e., age, gender, tumor side, tumor size (T1-T4 according to the Hannover classification), and hearing impairment (Gardner-Robertson classification, GR1-5), using a binary logistic regression.61.8% of patients complain about a preoperative tinnitus. The binary logistic regression analysis identified male gender [OR 1.90 (1.25-2.75); p = 0.002] and hearing impairment GR3 [OR 1.90 (1.08-3.35); p = 0.026] and GR4 [OR 8.21 (2.29-29.50); p = 0.001] as positive predictors. In contrast, patients with large T4 tumors [OR 0.33 (0.13-0.86); p = 0.024] and complete hearing loss GR5 [OR 0.36 (0.15-0.84); p = 0.017] were less likely to develop a tinnitus. Yet, 60% of the patients with good clinical hearing (GR1) and 25% of patients with complete hearing loss (GR5) suffered from tinnitus.These data are good accordance with literature about non-VS tinnitus indicating hearing impairment as main risk factor. In contrast, complete hearing loss appears a negative predictor for tinnitus. For the first time, these findings indicate a non-linear relationship between hearing impairment and tinnitus in unilateral sporadic VS. Our results suggest a similar pathophysiology in VS-associated and non-VS tinnitus.

Project description:Bilateral vestibular schwannoma is the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with a lifetime of surgical interventions, radiotherapy and off-label use of the anti-angiogenic drug bevacizumab. Unilateral vestibular schwannoma develops sporadically in non-NF2-related schwannomatosis patients for which there are no drug treatment options available. Tumour-infiltrating immune cells such as macrophages and T-cells correlate with increased vestibular schwannoma growth, which is suggested to be similar in sporadic and NF2-related schwannomatosis tumours. However, differences between NF2-related schwannomatosis and the more common sporadic disease include NF2-related schwannomatosis patients presenting an increased number of tumours, multiple tumour types and younger age at diagnosis. A comparison of the tumour microenvironment in sporadic and NF2-related schwannomatosis tumours is therefore required to underpin the development of immunotherapeutic targets, identify the possibility of extrapolating ex vivo data from sporadic vestibular schwannoma to NF2-related schwannomatosis and help inform clinical trial design with the feasibility of co-recruiting sporadic and NF2-related schwannomatosis patients. This study drew together bulk transcriptomic data from three published Affymetrix microarray datasets to compare the gene expression profiles of sporadic and NF2-related schwannomatosis vestibular schwannoma and subsequently deconvolved to predict the abundances of distinct tumour immune microenvironment populations. Data were validated using quantitative PCR and Hyperion imaging mass cytometry. Comparative bioinformatic analyses revealed close similarities in NF2-related schwannomatosis and sporadic vestibular schwannoma tumours across the three datasets. Significant inflammatory markers and signalling pathways were closely matched in NF2-related schwannomatosis and sporadic vestibular schwannoma, relating to the proliferation of macrophages, angiogenesis and inflammation. Bulk transcriptomic and imaging mass cytometry data identified macrophages as the most abundant immune population in vestibular schwannoma, comprising one-third of the cell mass in both NF2-related schwannomatosis and sporadic tumours. Importantly, there were no robust significant differences in signalling pathways, gene expression, cell type abundance or imaging mass cytometry staining between NF2-related schwannomatosis and sporadic vestibular schwannoma. These data indicate strong similarities in the tumour immune microenvironment of NF2-related schwannomatosis and sporadic vestibular schwannoma.

Project description:ImportanceAlthough numerous studies have evaluated the influence of advanced age on surgical outcomes following vestibular schwannoma (VS) resection, few if any large-scale investigations have assessed the comparative prognostic effects of age and frailty. As the population continues to age, it is imperative to further evaluate treatment and management strategies for older patients.ObjectiveTo conduct a population-based evaluation of the independent associations of chronological age and frailty (physiological age) with outcomes following VS resection.Design, setting, and participantsIn this large-scale, multicenter, cross-sectional analysis, weighted discharge data from the National Inpatient Sample were searched to identify adult patients (≥18 years old) who underwent VS resection from 2002 through 2017 using International Classification of Diseases, Ninth Revision, Clinical Modification and Tenth Revision, Clinical Modification codes. Data collection and analysis took place September to December 2020.Main outcomes and measuresComplex samples regression models and receiver operating characteristic curve analysis were used to evaluate the independent associations of frailty and age (along with demographic confounders) with complications and discharge disposition. Frailty was evaluated using the previously validated 11-point modified frailty index (mFI).ResultsAmong the 27 313 patients identified for VS resection, the mean (SEM) age was 50.4 (0.2) years, 15 031 (55.0%) were women, and 4720 (21.0%) were of non-White race/ethnicity, as determined by the National Inpatient Sample data source. Of the included patients, 15 090 (55.2%) were considered robust (mFI score = 0), 8204 (30.0%) were prefrail (mFI score = 1), 3022 (11.1%) were frail (mFI score = 2), and 996 (3.6%) were severely frail (mFI score ≥3). On univariable analysis, increasing frailty was associated with development of postoperative hemorrhagic or ischemic stroke (odds ratio [OR], 2.44 [95% CI, 2.07-2.87]; area under the curve, 0.73), while increasing age was not. Following multivariable analysis, increasing frailty and non-White race/ethnicity were independently associated with both mortality (adjusted OR [aOR], 2.32 [95% CI, 1.70-3.17], and aOR, 3.05 [95% CI, 1.02-9.12], respectively) and extended hospital stays (aOR, 1.54 [95% CI, 1.41-1.67], and aOR, 1.71 [95% CI, 1.42-2.05], respectively), while increasing age was not. Increasing frailty (aOR, 0.61 [95% CI, 0.56-0.67]), age (aOR, 0.98 [95% CI, 0.97-0.99]), and non-White race/ethnicity (aOR, 0.62 [95% CI 0.51-0.75]) were all independently associated with routine discharge.Conclusions and relevanceIn this cross-sectional study, findings suggest that frailty may be more accurate for predicting outcomes and guiding treatment decisions than advanced patient age alone following VS resection.

Dataset Information

Elevated baseline C-reactive protein levels predict poor progression-free survival in sporadic vestibular schwannoma.

Background

Methods

Results

Conclusions

Publications

Elevated baseline C-reactive protein levels predict poor progression-free survival in sporadic vestibular schwannoma.

Similar Datasets

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