In this week’s Case Record of the Massachusetts General Hospital, a 54-year-old man had transient then persistent partial loss of vision. Images of the brain showed two adjacent masses in the left occipital and posterior parietal regions. A diagnostic procedure was performed.
Glioblastoma is a highly malignant tumor, with a median survival of 9 to 14 months and 5-year survival in less than 10% of patients.
• What is the benefit of resection in a suspected case of glioblastoma?
Resection of a suspected malignant brain tumor confers several benefits. A resection specimen provides representative tumor tissue for pathological diagnosis, including molecular genetic tests. A debulking resection may also reduce mass effect and intracranial pressure, leading to clinical improvement and decreasing the need for antiedema medications such as glucocorticoids. A prospective, randomized trial showed that, in a subset of patients with glioblastoma, gross total resection conferred a survival benefit as compared with subtotal resection.
• How does the status of methylguanine-DNA methyltransferase (MGMT) methylation affect the prognosis of glioblastoma?
MGMT is a DNA-repair protein; the methylation status of the MGMT promoter has prognostic and potentially predictive significance in glioblastoma. Studies of the methylation status of the MGMT promoter in primary and recurrent glioblastomas have shown that recurrent tumors may change their methylation status, particularly if the primary tumor had a methylated MGMT promoter; however, methylation status of the MGMT promoter at recurrence does not appear to be predictive of subsequent outcome. In one study, patients with glioblastoma whose tumors were positive for MGMT methylation had a median survival of 21.7 months and 2-year survival of 46%, as compared with patients whose tumors were negative for MGMT methylation, who had a median survival of 12.7 months and 2-year survival of 13.8%.
Morning Report Questions
Q: What is the standard of care for patients with newly diagnosed glioblastoma?
A: Radiation was shown in the 1970s and 1980s to be superior to supportive care or chemotherapy alone in prolonging survival and is a critical component of the management of glioblastoma. Radiation is delivered as focal, fractionated, external-beam treatments. Temozolomide is an oral methylating agent that improves progression-free and overall survival as compared with radiation alone. It is administered concurrently with radiation for 6 weeks (chemoradiation) and then without radiation for 6 months. This regimen is now considered the standard of care for patients with newly diagnosed glioblastoma, regardless of the methylation status of MGMT.
Q: What is tumor pseudoprogression?
A: Tumor pseudoprogression is a reaction of the tumor and tumor microenvironment to radiation and chemotherapy. In one case series of glioblastoma, patients with tumors that showed pseudoprogression had improved survival relative to patients with tumors that did not develop pseudoprogression. Tumor pseudoprogression usually occurs within 3 months after completion of radiation and chemotherapy. Pseudoprogression occurs in approximately 20 to 40% of patients with glioblastoma after chemoradiation. Pseudoprogression may be associated with cerebral edema and increased intracranial pressure and can result in neurologic symptoms and signs.