Prognostic Factors in a Large Cohort of Patients with Glioblastoma
Abstract & Commentary
By Adília Hormigo, MD, PhD, Attending Neurologist, Memorial Sloan-Kettering Cancer Center, and Assistant Professor of Neurology, Weill Medical College of Cornell University. Dr. Hormigo reports no financial relationships relevant to this field of study.
Synopsis: This large retrospective study reports an overall poor prognosis for patients with GBM, but treatment was not "state-of-the-art."
Source: Helseth R, et al. Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. Acta Neurol Scand DOI:10.1111/j.1600-0404.2010.01350.x.
Glioblastoma (GBM) is the most common and malignant of all primary brain tumors. The initial standard treatment is resection followed by radiotherapy with concurrent chemotherapy with temozolomide and then adjuvant temozolomide. The median survival with treatment is about 12-14 months. However, in patients whose tumor tissue contains promoter methylation of MGMT (O6-methylguanine–DNA methyltransferase) DNA repair gene, survival can reach 24 months. The epigenetic silencing of this gene renders the tumor to be sensitive to alkylating agents.
In this paper, the authors retrospectively reviewed the cases of 516 consecutive patients who underwent the initial surgery for their GBM at Oslo University Hospital between the years 2003 and 2008. The median overall survival for those patients was 9.9 months. The authors identified as poor prognostic factors age greater than 60, poor neurological function, bilateral brain involvement, biopsy instead of resection, and adjuvant treatment with radiotherapy without concomitant use of chemotherapy with temozolomide. Sixty-five patients (13%) underwent repeat surgery and had an overall survival of 18.4 months. The indications for reoperation were worsening of neurological deficits (35.4%), raised intracranial pressure (33.8%), tumor progression on MRI (20%), and seizures (11%).
Commentary
This is a large, single-institution, retrospective study looking at prognostic factors for GBM. Analysis in such studies has limitations found in all retrospective work. Specifically for this study, the regimen of radiotherapy changed during the course of the years, from a total dose of 48 Gy given in two daily fractions to a more conventional daily treatment to a total of 60 Gy. This may be one of the reasons accounting for their low overall survival. We also do not know the extent of resection for the patients who underwent surgery and not just biopsy of their tumor. Post-operative MRI was not performed initially in the study in over half of the patients. The treatment regimen was not consistent, with only about half the patients having received radiotherapy with concurrent chemotherapy. The treatment was less aggressive for the elderly and it has been shown that at least the use of radiation for patients 70 and older has significant survival benefit without worsening of quality of life and cognition. The state of the art of analysis of MGMT promoter methylation status in tissue blocks, for purpose of determination of prognosis for survival was not performed in any group of patients. The improved survival on patients who underwent reoperation is most likely the result of several factors, including selection for surgery of patients whose tumor is still amenable to surgical resection, better performance status and younger age. It is unclear, in patients whose indication for surgery was seizures, what type of surgery they had, whether reoperation for the tumor, or surgery for epilepsy, and if it was or was not beneficial.
This study confirms the factors known to influence survival. We will only be able to further clarify prognostic factors for GBM by conducting prospective trials.
References
- Hegi ME, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Eng J Med 2005;352:997-1003.
- Keime-Guibert F, et al. Radiotherapy for glioblastoma in the elderly. N Eng J Med 2007;356:1527-1535.
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