What is the prognosis of glioblastoma multiforme (GBM)?

Updated: Jul 01, 2019
  • Author: Jeffrey N Bruce, MD; Chief Editor: Herbert H Engelhard, III, MD, PhD, FACS, FAANS  more...
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Answer

Only modest advancements in the treatment of glioblastoma have occurred in the past 25 years. Although current therapies remain palliative, they have been shown to prolong quality survival. Mean survival is inversely correlated with age, which may reflect exclusion of older patients from clinical trials. Without therapy, patients with glioblastoma multiformes uniformly die within 3 months. Patients treated with optimal therapy, including surgical resection, radiation therapy, and chemotherapy, have a median survival of approximately 12 months, with fewer than 25% of patients surviving up to 2 years and fewer than 10% of patients surviving up to 5 years. Whether the prognosis of patients with secondary glioblastoma is better than or similar to the prognosis for those patients with primary glioblastoma remains controversial.

Brain tumor resection has an overall mortality rate of 1-2%.  Approximately 40% of patients have no or minimal deficits after surgery, 30% manifest no postoperative change relative to preoperative deficits, and 25% sustain an increased postoperative deficit that usually improves.

Despite extensive clinical trials, individual prediction of clinical outcome has remained an elusive goal. Glioblastomas are among the most malignant human neoplasms, with a median survival despite optimal treatment of less than 1 year. In a series of 279 patients receiving aggressive radiation and chemotherapy, only 5 of 279 patients (1.8%) survived longer than 3 years. [42]

Patient survival depends on a variety of clinical parameters. Younger age, higher Karnofsky performance scale (a standard measure of the ability of patients with cancer to perform daily tasks) score at presentation, radiotherapy, and chemotherapy all correlate with improved outcome. Clinical evidence also suggests that a greater extent of resection favors longer survival. [43, 44, 45, 46] Tumors that are deemed unresectable due to location (eg, in the brainstem) also portend a poorer prognosis. [47]

A review by Perrini et al of 48 patients with recurrent glioblastoma found that preoperative performance status at recurrence and subtotal versus gross-total repeat resection were independent predictors of survival. These authors concluded that gross-total resection at repeat craniotomy is associated with longer overall survival and should be performed whenever possible in patients with recurrent glioblastoma who have good performance status. [48]

Survival has not been shown to correlate with p53, EGFR, or MDM2 mutations. [49]

Two separate reviews of outcomes in elderly patients have been published. One found that although elderly patients have a poor prognosis, gross-total resection confers a modest survival benefit and treatment with bevacizumab significantly increased overall survival. Older age and preoperative Karnofsky Performance Scale score also were significant prognostic factors. [50]

The results of the second study concurred that there is a survival advantage for those who undergo maximal safe resection. The review also found that radiotherapy extends survival in selected patients and temozolomide chemotherapy is safe and extends the survival of patients with tumors that harbor O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation. [51]

A study by Li et al used an updated Radiation Therapy Oncology Group (RTOG) GBM database to produce a simplified original recursive partitioning analysis (RPA) model combining classes V and VI. This resulted in 3 distinct prognostic groups defined by performance status, age, neurologic function, and extent of resection. This classification will be used in future RTOG GBM trials. [52]

Clearly, new approaches for the management of glioblastomas are necessary. Enrollment of patients into clinical trials will generate new information regarding investigational therapies. Novel approaches, such as the use of gene therapy and immunotherapy, as well as improved methods for the delivery of antiproliferative, antiangiogenic, and noninvasive therapies, provide hope for the future.

A study by Kaur et al determined that the presence of a large cyst in patients with GBM does not affect overall survival compared with those who do not have a cyst. [53]


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