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Treatment of High-Grade Gliomas in Elderly Patients
Abstract & Commentary
By Adília Hormigo, MD, PhD, Assistant Professor of Neurology, Weill Medical College, Cornell University. Dr. Hormigo reports no financial relationships relevant to this field of study.
Synopsis: Elderly patients with glioblastoma, who are independent in activities of daily living, will have a longer survival with good quality of life if treated with radiotherapy rather than supportive care, alone.
Source: Keime-Guibert F, et al. Radiotherapy for glioblastoma in the elderly. N Eng J Med. 2007;356:1527-1535
Most of the protocols for treatment of brain tumors exclude the elderly population. A concern for those that treat these patients is a potential increase in toxicity related to the treatment with cognitive deterioration and decrease of quality of life. A multicenter study was conducted in France, to compare radiotherapy treatment to supportive care in elderly patients with a high-grade glioma. Patients at the age of 70 or older with newly diagnosed anaplastic astrocytoma or glioblastoma multiforme, who underwent a resection, and had a Karnofsky performance score of 70 or higher were eligible to enroll. Diagnosis was confirmed by central review. Patients were randomized to focal radiotherapy in a daily fraction of 1.8 Gy, 5 days a week, to a total dose of 50 Gy or to supportive care alone, consisting of corticosteroids, anti-convulsant agents, physical and psychological support, and palliative care treatment. All patients who received radiotherapy tolerated it well and had no severe adverse effect from radiotherapy. Eighty-one patients with glioblastoma and 2 patients with anaplastic astrocytoma were enrolled. The median age was 73 for those patients who received supportive care alone and 75 for those who received radiotherapy. The median length of time from diagnosis to the start of radiation was 5.3 weeks. The median survival for the 39 patients who received radiotherapy was 29.1 weeks and 19.9 weeks for 42 patients who received supportive care alone. The median progression-free survival was 14.9 weeks with radiotherapy and supportive care and 5.4 weeks with supportive care alone. The median survival benefit for the group who received radiotherapy was 12.2 weeks greater than the group that received supportive care alone. Through their statistical analysis, the authors also showed that the survival benefit of radiotherapy was independent of the extent of the surgery. The Mini-Mental examination score declined over time in both groups, but there was no significant difference between the 2. Measures of quality of life also showed no significant differences. The trial was discontinued at the first interim analysis because of the advantage of radiotherapy over supportive care alone. The authors conclude that there was improvement in median survival for older patients with glioblastoma multiforme who underwent radiotherapy without reducing the quality of life or cognition.
This multi-center trial conducted in France compared radiotherapy to supportive care alone in patients 70 or older with high grade glioma. Since they only accrued two patients with anaplastic astrocytoma, their recommendation is for patients with glioblastoma multiforme. A significant benefit of radiotherapy was found at first interim analysis and thus the study was stopped. The study showed a similar decline in Karnofsky performance status over time within the 2 groups and no difference in quality of life measures. The conclusion from this study is that treatment with radiotherapy should be offered to the elderly patients who are able to care for themselves because it is well tolerated and has significant survival benefit.
In younger patients, the current standard treatment for a high-grade glioma is radiotherapy with concurrent temozolomide chemotherapy, followed by chemotherapy with temozolomide alone. One would think that a potential follow up study in the elderly with glioblastoma multiforme, would be to compare this regimen to radiotherapy alone, using the same primary endpoint of overall survival and secondary endpoints of progression-free survival, tolerance of the combined treatment, quality of life and cognition.
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