Barker, Fred G.

AbstractMeningioma is by far the most common primary intracranial tumor in adults. Treatment of meningioma is complex due to a tremendous amount of variability in tumor behavior. Many patients are incidentally found to have tumors that will remain asymptomatic throughout their lives. It is important to identify these patients so that they can be spared from potentially morbid interventions. On the other end of the spectrum, high-grade meningiomas can behave very aggressively. When treatment is necessary, surgical resection is the cornerstone of meningioma therapy. Studies spanning decades have demonstrated that extent of resection correlates with prognosis. Radiation therapy, either in the form of external beam radiation therapy or stereotactic radiosurgery, represents another important therapeutic tool that can be used in place of or as a supplement to surgery. There are no chemotherapeutic agents of proven efficacy against meningioma, and chemotherapy treatment is generally reserved for patients who have exhausted surgical and radiotherapy options. Ongoing and future studies will help to answer unresolved questions such as the optimum use of radiation in resected WHO grade II meningiomas and the efficacy of additional chemotherapy agents.

Purpose The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the clinical significance of GBM subtypes as defined by EGFRvIII status. Patients and Methods The expression of EGFRvIII was assessed by immunohistochemistry in 649 patients with newly diagnosed GBM. These data were then examined in conjunction with the expression of phospho-intermediates (in a subset of these patients) of downstream AKT and Ras pathways and YKL-40 as well as with known clinical risk factors, including the Radiation Therapy Oncology Group's recursive partitioning analysis (RTOG-RPA) class. Results The RTOG-RPA class was highly predictive of survival in EGFRvIII-negative patients but much less predictive in EGFRvIII-positive patients. These findings were seen in both an initial test set (n = 268) and a larger validation set (n = 381). Similarly, activation of the AKT/MAPK pathways and YKL-40 positivity were predictive of poor outcome in EGFRvIII-negative patients but not in EGFRvIII-positive patients. Pair-wise combinations of markers identified EGFRvIII and YKL-40 as prognostically important. In particular, outcome in patients with EGFRvIII-negative/YKL-40–negative tumors was significantly better than the outcome in patients with the other three combinations of these two markers. Conclusion Established prognostic factors in GBM were not predictive of outcome in the EGFRvIII-positive subset, although this requires confirmation in independent data sets. GBMs negative for both EGFRvIII and YKL-40 show less aggressive behavior.