The sex of a glioblastoma patient impacts their clinical outcome. Iron is a key metabolic driver in glioma biology impacting both neoplastic cells directly and tumor progression through the immune system.

Connor and colleagues identified a new function in iron delivery for a protein called ferritin that operates in a sex-specific fashion.

High expression of ferritin is known to be associated with poor overall survival in glioblastoma patients.

The Connor lab is actively investigating sex-dependent uptake of ferritin and whether blocking expression of ferritin in tumor cells might increase their sensitivity to treatment.

The other key factor in understanding the iron signature of glioblastomas is their gene expression profiles.

Members of the Connor Lab are investigating if there are sex-specific differences in the expression of iron metabolism-related genes.

Gene profiling revealed that some members of the immune cell family within tumors may be determining sex-related outcomes.

The lab continues to investigate how manipulating these immune cells might change the iron signature of tumors with the ultimate goal of improving prognosis for glioblastoma patients.

Analyzing cerebrospinal fluid for tumor cells has been the standard method for diagnosing neoplastic meningitis.

While this method is specific, it is only 50 percent sensitive. Magnetic resonance imaging (MRI) is another method used to diagnose this disease, but the sensitivity and specificity of MRI have not been established, and the ability of MRI scanning to predict outcomes is also unknown.

Using data from the International Neoplastic Meningitis Registry, which is managed by Penn State College of Medicine, researchers investigated the difference in outcomes between the two diagnostic techniques. They learned that patients diagnosed by various combinations of cytology and MRI positivity had different survival.

These findings have implications for patient care, clinical trial design and interpretation and discussions about prognosis.

Novel diagnostic strategies for neoplastic meningitis being developed by these same researchers are being subjected to a similar analysis.

The standard of care for treating neoplastic meningitis is to use radiation therapy for specific sites where symptoms occur, followed by delivery of chemotherapy directly into the spinal fluid by way of a ventricular catheter (an Ommaya reservoir), a technique which allows drugs to circumvent the blood-brain barrier.

The current standard of care for patients with neoplastic meningitis (in contrast to the approach for most patients with cancer outside of the nervous system) calls for administering a single drug into the spinal fluid.

Researchers at Penn State College of Medicine compared this single-agent approach to a multi-agent approach and found that patients who received multi-agent therapy had a dramatically improved survival and similar or reduced toxicity compared to those receiving single-agent therapy.

Neoplastic meningitis causes a variety of symptoms, including headaches, nausea, vomiting and fatigue and focal neurologic dysfunction.

Approximately 10 percent of patients experience what researchers at Penn State College of Medicine have termed “plateau wave events.”

While these events may mimic seizures, seizure medications are ineffective for this problem.

Plateau wave events are caused by abrupt increases in intracranial pressure, which cause patients to lose consciousness and motor tone. Reducing intracranial pressure through ventriculoperitoneal shunting results in immediate symptom resolution.