Prognostic Analysis And The Evaluation Of T-lymphocyte Subset On Immune State In Meningeal Carcinomatosis

Objective: Meningeal carcinomatosis(MC)is a disease that malignant tumor cells cultivate in the cerebrospinal fluid or meninges.With the development of therapy methods and new techniques,survival time of patients with tumor is prolonged,and the incidence of MC is increasing.At present,there is little probability that it will be cured.Therefore,improve patient neurological function and prolong their survival is the ultimate objective.We aimed to investigate the clinical features of MC,to identify prognostic factors related to MC survival and to evaluates immune state.Methods: A retrospective analysis of 35 cases who were diagnosed of MC with cerebrospinal fluid cytology or neuroradiological evidences in the Second Hospital of Hebei Medical University from January 2016 to January 2017 was made with follow-up studies.The prognosis of MC and the impact of age,initial KPS,primary tumor,initial CSF protein level,hydrocephalus,magnetic resonance imaging(MRI)enhancement scanning characteristics,therapy regiment and the dose of methotrexate were analysed.To use flow cytometry that detected the periphery blood and cerebrospinal fluid T-lymphocyte subset of them,and for comparison and analysis.Results:1 MC was predominantly seen in middle and aged patients and started in a subacute way.Distribution of diseases have been discovered in Shijiazhuang area,Hebei Province,was the common area of this disease occurrence.The primary tumor was lung cancer which was the most common in 20,gastric cancer in 7,unknown cancer in 4,breast cancer in 1,ovarian cancer in 1,prostate cancer in 1,lymphoma in 1.The main clinical features of MC were presented as manifestation of high intracranial pressure in 28 patients,cranial nerve injury in 21 patients presented with decreased vision,diplopia and hypoacusia,spinal cord or spinal nerve injury in 12 patients with cervicodorsal pain,limb weakness and uroschesis.Gait alterations could be caused by cerebellar dysfunction in 1 patients.The cerebrospinal fluid(CSF)of 35 patients with MC was investigated,which showed the tumor cells for the first time in 30 cases(85.7%).Magnetic resonance imaging(MRI)contrastenhanced scanning found abnormally diffused piamater enhancement in 13 cases out of 19,6 of which showed brain parenchyma reinforced mass.Genetic testing was performed in 18 cases.An exon 21 point mutation and an exon 19 deletion of EGFR were found in 6 patients respectively and T790 M mutation in 3 cases.2 23 patients received standard intrathecal chemotherapy regimen.Cytological analysis of(CSF)tumor cells turned negative from positive in 11 cases,and negative transformation rate of tumor cells were 47.8%.8 patients received standard intrathecal chemotherapy with 15 mg of methotrexate and 15 patients received standard intrathecal chemotherapy with 10 mg of methotrexate.The symptom remission rate in the groups were 87.50% and 33.33%,there was significant differences between two groups(P=0.027).3 At final follow-up on January 1,2017,17 patients were living,18 patients died.The median survival of the 35 cases was 7.54 months.Univariate analysis showed that the predictors of survival were primary tumor(P<0.001),hydrocephalus(P=0.014),initial KPS(P=0.001),and the therapy regiment(P =0.001).Multivariate analysis showed that KPS is an independent influential factor.4 T-lymphocyte subset in periphery blood and cerebrospinal fluid were determined in 16 patients.The level of CD8 in periphery blood was significantly higher than the normal range(P<0.05).There was no significant difference in CD3,CD4,CD4/CD8 in periphery blood between the normal range and MC patients(P>0.05).Compared with the normal range,the level of CD3,CD4,CD8 in cerebrospinal fluid were obviously elevated,CD8 was obviously reduced and had significant difference(P<0.05).The level of CD3,CD4,CD8 in cerebrospinal fluid was significantly higher than the level in periphery blood(P<0.05),but there was no differences in CD4/CD8(P>0.05).Conclusion:1 MC was predominantly seen in middle and aged patients and started in a subacute way.Distribution of diseases have been discovered in Shijiazhuang area,Hebei Province,was the common area of this disease occurrence.The primary tumor was lung cancer.The clinical presentations of MC are much complicated without specificity.Cytological examination of CSF is considered the golden standard for diagnosing this disease.MRI enhancement scanning contributed to early stage diagnosis of MC.Detection of gene mutation maybe benefit to the predicting prognosis and selection treatment drug.2 Intrathecal chemotherapy with 15 mg of methotrexate could effectively improve the clinical symptoms of patients with MC.Therefore,this approach is recommended in clinical depending on patients’ case condition.3 Primary tumor,hydrocephalus,initial KPS and the therapy regiment were related to the prognosis of patients with MC.KPS is an independent influential factors.4 Measuring T lymphocytes subsets is a powerful tool for evaluating cellular immune function of patients with MC,which be helpful in the evaluation of immune status in MC patients.