Clinical Features And Prognostic Factors In Patients With Leptomeningeal Metastases Of Solid Tumors

BackgroundThe incidence of leptomeningeal metastases in solid tumor patients is about 4%to 15%,ranking third in the central nervous system metastatic tumor,with a high mortality rate and poor prognosis.With the prolongation of survival of tumor patients and the advancement of imaging technology,the incidence rate has increased year by year.Although it has been reported for more than 140 years,the research progressed slowly.The main clinical manifestations are central nervous system symptoms.Diagnosis relies on clinical manifestations,cerebrospinal fluid cytology,and imaging studies,though they are less sensitive in early diagnosis of the disease.The treatments include intrathecal chemotherapy,systemic chemotherapy,whole brain and whole spinal cord radiotherapy,targeted therapy and anti-angiogenic drugs.The treatments are not ideal,and also have lots of treatment-related side effects.There are no unified guiding principles now.At present,there are few researches on solid tumor leptomeningeal metastases at home and abroad,and it is urgent to large sample data test to guide the clinical work.Methods149 cases of membrane cancer patients from Qilu Hospital and Provincial Hospital of Shandong University were collected during the period of 2003.1.1-2018.10.1,of which 25 patients were lost.Finally,124 cases were included in the study,and the data were obtained through case-based system and telephone visits.Information includes name,gender,age,primary tumor,ECOG-PS score,smoking and drinking history,clinical manifestations,lumbar puncture results,impact performance,overall survival(OS),and treatments.The obtained data were used to establish a database for follow-up.All patients were discontinued on October 1,2018.The overall survival was from the date of diagnosis to the date of death.Statistical analysis was performed on the data using SPSS22.0 statistical software.The correlation between the factors was analyzed by chi-square test,and the survival analysis was analyzed by Kaplan-Meier method and multi-factor COX proportional hazard model.P<0.05 was considered statistically significant.Results1.General information:A total of 124 patients with leptomeningeal metastases were collected,including 65 males and 59 females.The age is between 14-76 years old and the median age is 55 years old.The age of onset is more common in middle-aged and older people.Seventy-eight patients had a history of oncology,and 46 patients presented with a primary manifestation of neurological symptoms and signs.95 cases of lung cancer were the most common in the primary tumor(58 cases of NSCLC,3 cases of small cell lung cancer,34 cases were not explained),10 cases of breast cancer,12 cases of malignant tumors of the digestive tract,3 cases of tumors from other sources,and 4 cases of unknown primary tumor.PS score 0-2 points in 79 cases,3-4 points in 45 cases.A total of 48 patients with leptomeningeal metastases with intracranial metastases were enrolled;57 patients with bone,liver,lung and lymph nodes were transferred.2.Clinical manifestations:124 patients had intracranial hypertension,59 patients with LM only had symptoms and signs of intracranial hypertension,65 patients with LM also involved in the cranial nerve and spinal nerve symptoms and signs.3.Cerebrospinal fluid examination results:Lumbar puncture results showed different degrees of pressure increase,of which 44 patients were greater than 300 mm H20.108 in 111 patients found tumor cells in CSF;54 in 85 patients were elevated in CSF pressure,30 patients were normal,1 patient was reduced;52 in 86 cases were high and 34 cases were normal of CSF protein.4.Imaging findings:73 patients had enhanced MRI of the brain.Among them,9 patients with LM didn’t have obvious leptomeningeal metastases on MRI-enhanced scan,and 64 patients with LM showed that the meninges showed different degrees of enhancement.The main manifestations were linear,nodular or mixed abnormal signals in dura,pia,arachnoid and subarachnoid Spaces.Some patients were accompanied by varying degrees of ventricular dilatation,meningeal enhancement near the brain parenchyma edema or hydrocephalus and other phenomena.5.Treatment:The 124 patients with leptomeningeal metastases included in the group,61 patients received only symptomatic supportive therapy and 63 patients were given active treatment.Treatments include intrathecal chemotherapy,systemic chemotherapy,whole brain radiotherapy,targeted therapy,and anti-angiogenic drugs.The mean survival time of 124 patients was 12.81 months,and the overall median OS was 4.53 months.The median OS of the untreated patients was 1.43 months,and the median OS of the actively treated patients was 9.67 months.6.Univariate analysis showed that age(P=0.002),PS score(P<0.001),primary tumor(P<0.001),cerebrospinal fluid protein(P=0.005),and leptomeningeal metastases as the first diagnosis(P=0.002),other symptoms of intracranial hypertension(P = 0.043),combined treatment(P<0.001),systemic treatment(P<0.001),systemic chemotherapy(P = 0.029)in different groups has significant differences.Multivariate analysis showed that age,cerebrospinal fluid protein,and primary tumor were associated with prognosis in patients with LM(P<0.05).Conclusion1.Leptomeningeal metastases are the late stage of cancer.The clinical symptoms and signs are diverse and atypical.Cranial hypertension syndrome is more likely-to see in the early stage.Different degrees of cranial nerve and spinal nerve involvement are observed as the disease progresses.At present,the main treatments for solid tumor leptomeningeal metastases include intrathecal chemotherapy,systemic chemotherapy,whole brain radiotherapy,targeted therapy,and anti-angiogenic drugs,with poor prognosis and short survival.2.The primary source of tumor in this study was lung cancer,followed by digestive tract malignancy and breast cancer.3.MRI enhanced scan has great value for the diagnosis of LM.The patient is characterized by pia mater-subarachnoid enhancement,in which linear enhancement is mostly,while those with dura mater are mostly nodular enhancement.4.Most patients with LM have high cerebrospinal fluid pressure,increased protein content.Cytological diagnosis was highly specific but still false-negative.CSF cytology combined with MRI enhanced scan can improve the diagnosis rate of LM.5.Univariate analysis found that age>55 years,PS score>2 points,elevated cerebrospinal fluid protein,leptomeningeal metastases as the first diagnosis,involvement of cranial nerve and spinal nerve symptoms are factors lnfluencing the prognosis of patients with LM;systemic therapy,systemic chemotherapy and combination treatments can prolong the survival of LM patients;patients with different primary tumors have different prognosis.Multivariate analysis found that age,cerebrospinal fluid protein,and primary tumor were independent prognostic factors for leptomeningeal metastases.