PurposeCancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue.Materials and MethodsWe sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer.ResultsWe detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations.ConclusionThe study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.

Brain metastases (BMs) occur in 10% to 20% of adult patients with cancer, and with increased surveillance and improved systemic control, the incidence is likely to grow. Despite multimodal treatment, prognosis remains poor. Current evidence supports use of whole-brain radiation therapy when patients present with multiple BMs. However, its associated cognitive impairment is a major deterrent in patients likely to live longer than 6 months. In patients with oligometastases (one to three metastases) and even some with multiple lesions less than 3 to 4 cm, especially if the primary tumor is considered radiotherapy resistant, stereotactic radiosurgery is recommended; if the BMs are greater than 4 cm, surgical resection with or without postoperative whole-brain radiation therapy should be considered. There is increasing evidence that systemic therapy, including targeted therapy and immunotherapy, is effective against BM and may be an early choice, especially in patients with sensitive primary tumors. In patients with progressive systemic disease, limited treatment options, and poor performance status, best supportive care may be appropriate. Regardless of treatment goals, use of corticosteroids or antiepileptic medications is helpful in symptomatic patients. In this review, we provide a summary of current therapy, as well as developments in the treatment of BM from solid tumors.

The seven item risk score adequately identified mild stroke patients who are at an increased risk of developing PSCI.

We defined ≥1 CSF-CTC/mL as the optimal cutoff for diagnosis of LM. CSF-CTC enumeration through RCCT is a robust tool to diagnose LM and should be considered in the routine LM workup in solid tumor patients.