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|Year : 2021 | Volume
| Issue : 5 | Page : 1509-1510
Systemic Inflammatory Markers and Prediction of Meningioma Grade: What Have We Learnt So Far?
Arivazhagan Arimappamagan, Alok M Uppar
Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
|Date of Submission||19-May-2021|
|Date of Acceptance||06-Jul-2021|
|Date of Web Publication||29-Oct-2021|
Professor, Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore - 560 0029, Karnataka
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Arimappamagan A, Uppar AM. Systemic Inflammatory Markers and Prediction of Meningioma Grade: What Have We Learnt So Far?. Neurol India 2021;69:1509-10
Inflammation has been extensively researched in the field of cancer, with possible multifaceted roles as an inciting factor, catalyst, or a resultant effect of cancer. Recent studies have evaluated the significant role of host inflammatory response in the progression as well as the prognosis of cancer. Serum markers have been found very useful in cancers of the prostate, colon, ovary, and so on. Manjunath et al., in this issue, have analyzed the systemic inflammatory markers in a large cohort of meningioma and evaluated their potential role in predicting the grade of the tumor.
In the brain, the tumor microenvironment appears to play a significant role in the progression as well as response to therapy. It possibly contributes to the resistance to the existing radiotherapy and chemotherapy treatments. The tumor microenvironment often demonstrates infiltration by various inflammatory cells such as neutrophils and lymphocytes. Serum can be considered to reflect this enhanced inflammatory response due to brain tumor, and changes in the peripheral blood levels of such markers can be anticipated.
The directions of research are driven by the two considerations, namely, the possible reflection of inflammatory activity in tumor microenvironment in the peripheral blood and that this inflammatory response could vary among different tumors or within different grades of a tumor.
We shall look at the evidence so far and how it enhances the existing modalities of diagnosis. Kayhan et al. evaluated the preoperative inflammatory markers in a cohort of 140 patients, which included temporal lobe epilepsy, glioma, meningioma, and metastasis and compared with healthy controls. This study noted that neutrophil counts, platelet counts, neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio were significantly higher in glioma, meningioma, and metastasis patients as compared with epilepsy patients (P < 0.05). Furthermore, the platelet–lymphocyte ratio could differentiate metastasis from glioblastoma multiforme (GBM), albeit with only a sensitivity of 84% and low specificity (48%). Another study that included 750 patients with glioma, 44 with acoustic neuroma, 271 with meningioma, 102 with nonlesional epilepsy, and 682 healthy controls demonstrated that significantly higher preoperative absolute white blood cell, neutrophil, and monocyte counts were found in glioma patients than in the patients with other tumors as well as controls. On evaluating the differences between GBM and other grades of glioma, they demonstrated that NLR had the best accuracy for GBM diagnosis, with an area under the curve (AUC) of 0.811 (95% confidence interval 0.778–0.844), and this could be considered a discriminative parameter in predicting the grades of glioma.
Studies on meningioma are fewer, with less convincing results. As the magnetic resonance imaging of meningioma is mostly very sensitive for making a diagnosis in most cases, the point of interest here is the prediction of meningioma grade preoperatively. A higher-grade tumor is well-known to have poorer prognosis, and therefore surgical resection should be as radical as possible as the primary treatment. Lin et al. evaluated 14 different serum inflammatory markers in 672 patients with meningioma and concluded that they did not provide sufficient strength in predicting a higher-grade tumor preoperatively, with the highest diagnostic accuracy reaching up to 64%. A combination of red blood cells and derived NLR count demonstrated the highest AUC (0.60). Liang et al., evaluating 944 meningioma patients retrospectively, noted that higher leucocyte counts and lower LMR (lymphocyte–monocyte ratio) correlated with a higher grade of meningioma in multivariable analysis.
The article by Manjunath et al. in the current issue delves further in this direction. The authors retrospectively analyzed various serum inflammatory parameters in a cohort of 780 patients with meningioma treated in a single institute. They noted that the values of absolute neutrophil count, NLR, and derived NLR could weakly distinguish between low- and high-grade meningiomas, with sensitivity and specificity ranging from 31.3% to 44.74% and 65.92% to 83%, respectively, for different parameters.
These observations need to be interpreted from a clinical perspective and utility. First, it is interesting and encouraging to look for a preoperative marker that can predict a higher-grade meningioma, thereby influencing surgical excision. However, the data from serum inflammatory markers are yet to be conclusive and need further exploration. As noted in the above studies, a higher neutrophil count could indicate a higher grade, but this response could be nonspecific and indicate the ongoing inflammation due to any number of reasons. Similar findings have been noted with other tumors too like glioma and metastasis, supporting the hypothesis that tumor is a proinflammatory condition. Second, the cutoffs and the diagnostic window for prediction of a higher-grade meningioma for these parameters are very narrow and can easily intersect with low-grade meningioma, thereby diminishing their clinical utility. This is further evident from the low AUC values for various parameters in these studies.
Lin et al. lucidly postulated the possible reasons for this limited ability of systemic inflammatory markers to predict meningioma grade as follows: (1) There is no sufficient evidence that a higher-grade meningioma results in more intense inflammatory response locally. (2) The inflammatory changes in tumor microenvironment may not be appropriately reflected in the peripheral blood, and these could be over- or underrepresented in the peripheral blood. (3) The serum inflammatory markers can be influenced by a number of other factors, including comorbidities and other associated treatments such as steroids.
The above three studies on meningioma are reasonably large and extensive, notwithstanding some limitations such as being retrospective in nature. Also, some clinical features such as male gender have been noticed to predict a higher-grade meningioma in these studies. Therefore, it is more likely that a composite signature that incorporates clinical and imaging markers in addition to the systemic inflammatory markers could provide a stronger biomarker that can predict a higher-grade meningioma with more accuracy. Future studies could possibly explore these integrated approaches in tumor diagnosis and grade prediction in meningioma.
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