Analysis Of Treatment And Prognostic Factors Of Meningeal Carcinomatosis

Meningeal carcinomatosis(MC) is also called neoplastic meningitis(NM), which is a devastating complication of systemic cancer with the dissemination or seeding of tumor cells to the meninx(dura mater, subarachnoid space and cerebral pia mater) and spinal meninges, about 5% ~ 10% of patients with tumors may develop MC, it is one of the important reasons for the death of advanced malignancies.The clinical manifestations of meningeal carcinomatosis are diversity, and the main symptoms are intracranial pressure(ICP) increased, followed by cranial nerve palsy, spinal nerve injury, cognitive dysfunction and so on.In recent years, with the continuous improvement of clinical knowledge and diagnosis technology, especially skull MRI scan has become the preferred noninvasive method,and has played an important role in the diagnosis of MC.At the same time, along with the application of radiotherapy and chemotherapy, and the emergence of new targeted therapy, the survival time of patients with MC has been prolonged. After chemotherapy or radiation therapy, some patients can prolong their life to 4 ~ 6 months.Therefore, earlydiagnosis and treatment is the key to prolong survival time and improve their prognosis of patients with MC, also can reduce clinical missed diagnosis and misdiagnosis.Despite the level of diagnosis and treatment in MC had increased, the treatment decisions may be always influnced, because of limited economic conditions or lack of treatment methods, resulting in poor treatment effects.Nevertheless, now about the study of pathogenesis and treatment options of MC are still few, and there are no available standard guidelines. In addition, we know very little about the prognostic factors of MC,which still have lots of controversial issues, and we haven't found detailed reports on prognostic factors of MC in China.To improve the level of understanding and diagnosis,and to provide a reasonable treatment of MC in the early stage,at the same time to prolong the survival time of patients as soon as possible,the clinical data of meningeal carcinomatosis was retrospectively reviewed and analysed, and the treatment and prognostic factors were studied in this article.ObjectivesThe clinical data of patients with MC was analyzed retrospectively, to investigate the significance of the clinical features, neuroimaging examination and cerebrospinal fluid(CSF) cytology examination in the diagnosis of MC; To improve the understanding of MC and reduce the clinical missed diagnosis and misdiagnosis,we explored the treatment options of MC for its influence on survival time and evaluated potential prognostic factors in the patients with MC.MethodsThe clinical data of 83 patients with meningeal carcinomatosis were analyzed retrospectively from xijiing hospital of fourth military medical university during2008.11~2015.8; the Kaplan-Meier survival curve was used to analyze and compare the survival time of patients with MC; the potential prognostic factors of MC were evaluated by univariate and multivariate analysis according to Cox proportional hazard regression.Results1. Meningeal carcinomatosis may occur in both male and femal, there was no obvious sex difference, the onset average age was 53.7�3.3, and the starting symptoms chiefly showed intracranial hypertension, including headache(73.5%), vomiting or nausea(59.0%), also could be accompanied by cranial nerve injury and spinal nerve lesions,and meningeal irritation signs(44.0%) or other symptoms.2. There was 65.1%(54/83) of patients with MC diagnosed by CSF cytology alone,13.3%(11/83) by MRI, and 21.6%(18/83) by both. Conventional MRI showed no evdent meningeal abnormalites.After enhancement scanning of 46 patients,63%(29/46)of patients had abnormal meningeal reinforcement,which were seen at pia-subarachnoid space 16 cases(56%), at abnormal dura-arachnoid 8 cases(28%) and all sides 5 cases(16%), according to the shape of the meninges reinforcement, the form of linear pattern was 14 cases, nodular pattern 8 cases and mixed pattern 7 cases.CSF examination revealed pressure elevated in 49 cases(72%),as well as CSF white blood cells in 45 cases(66%), protein in 42 cases(62%), and CSF glucose reduced in31 cases(45%), chlorine reduced in 10 cases(15%), 87%(72/83) of the patients with CSF cytology examination found malignant cells, and the positive rate of first lumbar puncture was 44.4%.3. Seventy-three cases(88%) were found the primary tumors by clinical features and pathology examination, 67 cases(81%) had solid tumors, including 31(38%) had lung cancer, 22(27%) had gastrointestinal cancer, 7(8%) had breast cancer and other solid tumors were 7 cases(8%); 6 cases(7%) had hematopoietic tumors, including 5 cases with lymphoma and 1 case with multiple myeloma;10(12%) patients with primary tumor was unknown.4. In our study,56%(46/83) of the patients had supportive therapy only,44%(37/83)received anti-tumor therapy, 31% had systemic chemotherapy(SC) alone, 3% received intrathecal chemotherapy(ITC), 1% had ITC combined with SC, 6% received whole brain radiotherapy(WBRT), and 4% received WBRT combined with SC. Overall mediansurvival time(OMST) was 11.8 weeks.The survival time of MC was associated with the type of primary tumor and treatment,the survival time was longer in hematological malignancies than solid tumors(P=0.014), 28 weeks and 10.2 weeks respectively. The survival time of systemic chemotherapy or systemic chemotherapy combined with other treatment methods was longer than unsystemic chemotherapy patients(P = 0.002), respectively 14.5 and 8.6 weeks.5. Univariate Cox regression analysis revealed that age >55 and decreased CSF glucose were poor prognosis for the patients with MC. Moreover, multivariate Cox regression analysis revealed systemic chemotherapy was a positive prognostic factor in patients with MC(RR 0.513,P=0.012).Conclusions1. Meningeal carcinomatosis usually occurred in the middle-aged and elderly, and the clinical manifestations of central nervous system were diversity and lack of specificity,the main findings were intracranial hypertention syndrome in the early stage,which easily led to misdiagnosis. Our case series showed that the most common primary tumor of MC was lung cancer,followed by gastrointestinal cancer, breast cancer and lymphoma of hematological malignancies.2. Enhanced MRI was one of the most important examinations for MC in the early stage,and could provide evidence for the diagnosis of MC, abnormal strengthening signals often displayed in pia-subarachnoid space,the abnormal meningeal nodular pattern or mixed pattern was the characteristic imaging manifestation for the diagnosis of MC.Abnormal changes of CSF biochemical examination were not specific, CSF cytology had low sensitivity for the first time, but still was the main means for the diagnosis of MC.3. In our study, the overall survival time was still shorter than the reports in abroad, and patients had poor prognosis with MC, the results of this study suggested that the application of systemic chemotherapy was a positive independent prognostic factor in patients, especially systemic chemotherapy alone or in combination with other therapeutic modal ITCies may prolong the survival time in patients with MC. Therefore,the appropriate treatment options and aggressive treatment have important significance to improve survival time in patients with MC.