Ha, Yooree

Abstract Background Cerebrospinal fluid cell-free DNA (cfDNA) can detect and monitor leptomeningeal disease but has not been previously used to monitor parenchymal lesions. Methods Herein, we report our initial experience with CSF cfDNA monitoring for 2 patients with colorectal cancer (CRC) metastases to the thalamus, causing obstructive hydrocephalus. Results CSF samples were obtained during ventriculoperitoneal shunt placement, demonstrating high levels of cfDNA in both cases. Several genomic alterations detected in the cfDNA sequencing matched those in the tumor tissue biopsy. Follow-up CSF evaluations after subsequent therapy were used to help adjudicate pseudo-progression versus true progression. Conclusions Neither patient developed leptomeningeal disease, demonstrating CSF’s utility in evaluating solitary brain metastases in direct contact with a CSF compartment.

OBJECTIVE Following resection of posterior superior frontal gyrus (PSFG) tumors, patients can experience supplementary motor area (SMA) syndrome consisting of contralateral hemiapraxia and/or speech apraxia. Given the heterogeneity of PSFG tumors, the authors sought to determine the risk of postoperative deficits and assess predictors of outcomes for all intraparenchymal PSFG tumors undergoing surgery (biopsy or resection), regardless of histology. METHODS This was a retrospective single-center cohort study of adult PSFG-region tumors undergoing biopsy or resection by a single surgeon. RESULTS A total of 106 consecutive patients undergoing 123 procedures (21 biopsies, 102 resections) fulfilled inclusion and exclusion criteria. Anaplastic astrocytomas were the most frequent among resected tumors (39% vs 29%), while glioblastomas were most common among biopsies (38% vs 27%) (p < 0.0001). The biopsy cohort was more likely to have tumor involvement outside the PSFG (90% vs 62%) (p = 0.011), most commonly in the motor cortex (67% vs 31%) (p = 0.005). Seizures were the most common presenting symptom in the resection cohort (p = 0.017), while motor deficits were more common in the biopsy cohort (58% vs 29%) (p < 0.001). Immediate postoperative neurological deficits occurred in 71 cases (58%), but only 3 of the deficits were permanent at 6 months of follow-up (2%). Postoperative SMA syndrome occurred in 48 cases (47%) and was significantly associated with involvement of the motor cortex (p = 0.018) or cingulate gyrus (p = 0.023), which were also significant in multivariate analysis as risk factors for SMA syndrome. However, postoperative SMA syndrome was not significantly associated with overall survival (p = 0.51). There were no perioperative deaths, but corpus callosum involvement (p < 0.001), contrast enhancement (p = 0.003), and glioblastoma pathology (p = 0.038) predicted worse overall survival in patients undergoing resection. CONCLUSIONS Nearly half of all patients undergoing resection of PSFG-region tumors experience a postoperative SMA syndrome. Individuals with corpus callosum and/or motor cortex involvement may be at an increased risk of experiencing SMA syndrome. However, these deficits are usually transient, and the risk of permanent new deficits is very low (3%). Preoperative characteristics including corpus callosum involvement and tumor enhancement—in addition to pathology—might serve as predictors of overall survival within this patient population.

Aberrant metabolism is a hallmark of malignancies including gliomas. Intracranial microdialysis enables the longitudinal collection of extracellular metabolites within CNS tissues including gliomas and can be leveraged to evaluate changes in the CNS microenvironment over a period of days. However, delayed metabolic impacts of CNS injury from catheter placement could represent an important covariate for interpreting the pharmacodynamic impacts of candidate therapies. Intracranial microdialysis was performed in patient-derived glioma xenografts of glioma before and 72 h after systemic treatment with either temozolomide (TMZ) or a vehicle. Microdialysate from GBM164, an IDH-mutant glioma patient-derived xenograft, revealed a distinct metabolic signature relative to the brain that recapitulated the metabolic features observed in human glioma microdialysate. Unexpectedly, catheter insertion into the brains of non-tumor-bearing animals triggered metabolic changes that were significantly enriched for the extracellular metabolome of glioma itself. TMZ administration attenuated this resemblance. The human glioma microdialysate was significantly enriched for both the PDX versus brain signature in mice and the induced metabolome of catheter placement within the murine control brain. These data illustrate the feasibility of microdialysis to identify and monitor the extracellular metabolome of diseased versus relatively normal brains while highlighting the similarity between the extracellular metabolome of human gliomas and that of CNS injury.