Liquid biopsy in the setting of leptomeningeal metastases: a systematic review and meta-analysis.

PURPOSE: The blood-brain barrier can prevent circulating tumor DNA (ctDNA) derived from the central nervous system from entering the blood making it challenging to evaluate molecular features of leptomeningeal metastasis (LM). Accordingly, we sought to systematically compare the diagnostic power or significance of ctDNA derived from cerebrospinal fluid (CSF) compared to plasma ctDNA in patients with LM. METHODS: A systematic review and meta-analysis was performed under the PRISMA guideline. We used PubMed, EMBASE, and the EuroPMC to search the literature using combinations of the following terms: circulating tumor DNA, ctDNA, circulating tumor cell, brain metastasis, leptomeningeal metastasis, outcome(s), and prognosis. We included all available English language studies that compared the diagnostic significance of CSF derived and serum ctDNA. All eligible studies level of bias was assessed using the New Castle Ottawa Scale (NOS). RESULTS: Our meta-analysis from 6 included studies (n = 226) that confirmed the diagnostic power of liquid biopsies in detecting genomic alteration is better when taking a CSF-derived samples than from the plasma (RR 1.46 [0.93; 2.29]; I2 = 92%; p-value < 0.01). CONCLUSION: CSF ctDNA is better at describing molecular landscape for LM; such an understanding may ultimately help inform patient treatment and responses to therapy.

Sustained Low-Efficiency Dialysis is Associated with Worsening Cerebral Edema and Outcomes in Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVES: We postulated that renal replacement therapy (RRT) in ICH patients with advanced chronic kidney disease (CKD) is associated with increased frequency and size of perihematomal edema (PHE) expansion and worse patient outcomes. METHODS: The Get With the Guidelines-Stroke Registry was queried for all patients admitted with ICH (N = 1089). Secondary causes, brainstem ICH, and initial HV < 7 cc were excluded. We identified patients with advanced CKD with and without RRT following admission for ICH. ABC/2 formula was used to measure hematoma volume (HV) and PHE. Patient outcomes were 30-day mortality, 90-day modified Rankin Scale score, and discharge disposition. We used propensity scores and optimal matching to adjust for multiple covariates. RESULTS: At 48 h post-ICH, PHE expansion was a significant predictor of poor patient outcomes in our cohort. Patients with CKD who received sustained low-efficacy dialysis (SLED) treatment had larger 48 h PHE growth compared to both untreated CKD group (average treatment effect (ATE), 11.5; 95% CI, 4.9-18.1; p < 0.01) and all untreated patients (ATE, 7.43; 95% CI, 4.7-10.2; p < 0.01). Moreover, patients with RRT had significantly worse functional and mortality outcomes. CONCLUSIONS: SLED treatment in ICH patients with CKD was associated with significant increase in rate and frequency of PHE expansion. Absolute increase in PHE during 48-h post-ICH was associated with increased mortality and worse functional outcomes. Further prospective and multicenter evaluation is needed to differentiate the effects of RRT on hematoma dynamics and patient outcomes from those attributed to CKD.