P05.24 The diagnosis and comprehensive treatment of leptomeningeal metastases--results of a phase II trial

Abstract

A prospective phase II trial was conducted to investigate the diagnosis of leptomeningeal metastases (LMs) and clinical outcomes of comprehensive treatment. Patients who were clinically suspected to have LMs and received comprehensive treatment based on Tomotherapy were enrolled. Whole brain radiotherapy (WBRT) with or without simultaneously boost to LM or craniospinal irradiation (CSI) was given to them. The diagnosis and response were assessed by the results of enhanced MRI, clinical symptoms and signs, cerebrospinal fluid (CSF) cytology, liquid biopsy and liquid genomics detection. The primary endpoint was local control (LC), and the secondary endpoints were intracranial progression-free survival (IPFS) and overall survival (OS). From 2014 to 2017, 88 patients were enrolled (Male: Female=36:52), and the median age was 55 years old (range, 29–81). The major primary diagnosis was NSCLC (64.8%). Typical clinical signs included cerebral (70.5%), cranial nerve palsies (30.7%), and spinal complaints (33.0%). 20.5% of patients showed no obvious symptoms. MRI findings before treatment included 4 types: multiple brain metastases (BMs) with focal LMs, large BMs invaded meningeal, extensive LMs and LMs proved by clinical symptoms or CSF without changes in MRI. The lesions appeared as nodular (67.1%), linear enhancement (18.2%), both (10.2%), or narrowing brain fold without other appearance (4.5%). MRI changes after radiation mainly included decreased lesions and weakened enhancement (65.9%), increased and strengthened followed by decreased lesions and weakened enhancement (18.2%), and increased lesions and strengthened enhancement but with cystic change (5.7%). 9 patients were diagnosed with distinct spinal cord metastases. 31 patients received lumbar puncture, and CSF cytology mainly showed increased leukocyte counts (64.5%), evaluated protein (54.8%) and decreased glucose (51.6%). Tumor cells were found in 19 patients, who were administrated intrathecal chemotherapy (mostly methotrexate; the median cycles were 4), in which 9 turned to be negative. 4 patients received CSF genetic testing and 2 had mutation.Patients received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60 Gy in 20 f for boost; 64.8%), focal radiation to LMs (26.2%), WBRT and CSI (50 Gy in 25 f for WBRT and 36 Gy in 20 f for CSI; 9.1%). Response rates of CR, PR and SD were 5.7%, 71.6% and 13.6%, respectively. The median follow-up and survival time was 13.5 and 17.6 months, respectively. The 1-year LC, IPFS and OS was 75.2%, 52.9%, and 71.3%, respectively. Neuroimaging, clinical signs and CSF findings may be prior inspection items for diagnosis of LMs. Early detection with reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted agents can improve local control and survival time of these patients.