S100B is a protein biomarker that reflects CNS injury. It can be measured in the CSF or serum with readily available immunoassay kits. The excellent sensitivity of S100B has enabled it to confirm the existence of subtle brain injury in patients with mild head trauma, strokes, and after successful resuscitation from cardiopulmonary arrest. The extent of S100B elevation has been found to be useful in predicting clinical outcome after brain injury. Elevations of S100B above certain threshold levels might be able to reliably predict brain death or mortality. A normal S100B level reliably predicts the absence of significant CNS injury. The specificity of S100B levels as a reflection of CNS injury is compromised by the findings that extra-cranial injuries can lead to elevations in the absence of brain injury. This potential problem can most likely be avoided by measuring serial S100B levels along with other biomarkers and carefully noting peripheral injuries. Serum markers GFAP and NSE are both more specific for CNS injury and have little to no extra-cranial sources. Sustained elevations of S100B over 24 h along with elevations of GFAP and NSE can more reliably predict the extent of brain injury and clinical outcomes. In the future, S100B measurements might reliably predict secondary brain injury and enable physicians to initiate therapeutic interventions in a timelier manner. S100B levels have been shown to rise hours to days before changes in ICP, neurological examinations, and neuroimaging tests. S100B levels may also be used to monitor the efficacy of treatments.

Toca 511 (vocimagene amiretrorepvec) is an investigational nonlytic, retroviral replicating vector (RRV) that delivers a yeast cytosine deaminase, which converts subsequently administered courses of the investigational prodrug Toca FC (extended-release 5-fluorocytosine) into the antimetabolite 5-fluorouracil. Forty-five subjects with recurrent or progressive high-grade glioma were treated. The end points of this phase 1, open-label, ascending dose, multicenter trial included safety, efficacy, and molecular profiling; survival was compared to a matching subgroup from an external control. Overall survival for recurrent high-grade glioma was 13.6 months (95% confidence interval, 10.8 to 20.0) and was statistically improved relative to an external control (hazard ratio, 0.45; P = 0.003). Tumor samples from subjects surviving more than 52 weeks after Toca 511 delivery disproportionately displayed a survival-related mRNA expression signature, identifying a potential molecular signature that may correlate with treatment-related survival rather than being prognostic. Toca 511 and Toca FC show excellent tolerability, with RRV persisting in the tumor and RRV control systemically. The favorable assessment of Toca 511 and Toca FC supports confirmation in a randomized phase 2/3 trial (NCT02414165).

Multiyear durable responses have been observed in rHGG patients treated with Toca 511 + Toca FC in a phase I trial, and the treatment will be further evaluated in a randomized phase III trial. Among IDH1 mutant patients treated at first recurrence, there may be an enrichment of complete responders.

The development of catheter associated granulomatous masses in intrathecal morphine therapy is an uncommon, but potentially serious problem. While these systems have historically been used in patients with short life expectancies, more recently patients with pain from a benign source have benefited from this therapy, and new complications are being encountered secondary to the patients' longer life spans. Morphine is the most commonly used intrathecal opioid and evidence exists that the formation of granulomatous masses are related to the use of higher doses. When the patients' requirement of morphine increases significantly, the physician should be alert for signs of spinal cord compression, such as new neurological deficits, myelopathy, or radiculopathy. Patients that require these higher doses should be properly informed of the association with granulomas and their associated risks. Indolent infection may also be the etiology of granulomatous masses, and the presence of organisms, both aerobic and anaerobic, should be routinely investigated. Patients with catheter-associated granulomas appear to share several features. They exhibit the onset of symptoms several months following the initiation of intraspinal opioids and commonly present with an increase in pain that precedes signs and symptoms of neurological deterioration. While MRI might be the preferred method of detection of intrathecal granulomas, its cost and availability are prohibitive for routine screening. CT myelogram via pump side port injection of contrast can also be performed to detect catheter tip related granulomas/obstructions. Serial neurological examinations for new deficits may be performed and recorded during pump refill visits to recognize a granulomatous mass in its early stages. If an abnormality is identified, imaging studies are appropriate. Awareness of the condition and vigilance are the keys to successful management of this complication.

We conclude that there is no long-term survival advantage of increased radiation dose with (125)I seeds in newly diagnosed glioma patients.