Management of High-Grade Gliomas in the Elderly☆
Section snippets
Case Study
An 84-year-old man presented with symptoms of difficulties with reading and writing and right-sided homonymous hemianopsia. Magnetic resonance imaging of the brain was performed, and the scan revealed a large heterogeneously enhancing mass within the left parietal-occipital lobe (Fig. A). A gross total resection was performed and results of the pathology revealed a glioblastoma (GBM). Postoperatively, he recovered well with a Karnofsky performance status (KPS) of 90. The patient was not
Background
GBM is the most common primary brain tumor in adults1 and has a profoundly poor prognosis. Although other high-grade histologies, such as anaplastic astrocytoma or oligodendroglioma, can present in adults, GBM becomes the most predominant with advancing age. High-grade glioma is therefore almost synonymous with GBM in the older age group. This is unfortunate, as even in the setting of very aggressive multimodality treatment, 5-year survival with GBM is only 10%.2 The disease is characterized by
Patterns of Practice
Older patients with GBM are less likely to receive standard therapy than their younger counterparts. Reasons for this might include the presence of comorbidities, an aggressive disease course with rapidly progressive loss of function and worsening cognition, and an anticipated shorter length of survival based on past experience.6, 7, 8, 9, 20 For example, population-based data, gathered from the Ontario Cancer Registry between 1982 and 1994, demonstrated age as a factor in several areas of
Surgery
GBM is a highly infiltrative malignancy, and complete resection of the tumor is not routinely possible. The current surgical approach is to remove as much gross tumor as safely possible, trying to limit postoperative neurologic deficits. Uncertainty previously existed about the use of debulking surgery over biopsy alone in elderly patients. A small prospective study of 30 patients older than 65 years, with grade III or IV glioma and a KPS > 60, was designed to address this question.21 Patients
Radiotherapy
The benefit of adjuvant radiotherapy in elderly patients has been firmly established by a series of prospective and retrospective clinical studies. Keime-Guibert et al24 published a randomized clinical trial, in which patients who are 70 years and older with high-grade glioma received only supportive care or involved-field radiotherapy at a dose of 50.4 Gy in 28 fractions following surgery. The primary end point was survival, but secondary end points included health-related quality of life and
Chemotherapy
As discussed, the current standard of care in elderly patients is surgery followed by radiotherapy. However, given the improvement in survival with the addition of temozolomide in nonelderly population, the use of chemotherapy is being explored in this population as well. Temozolomide could play a role in 2 different settings. The first is in the concurrent and adjuvant setting, if treatment escalation is felt to be beneficial and tolerable. The second is as a stand-alone adjuvant therapy as an
Molecular Prognostic Factors
A major biomarker identified in the EORTC-NCIC trial is the MGMT promoter methylation status, which identifies patients who may benefit from temozolomide. There are several reports in the literature of MGMT promoter methylation status in the elderly.45, 46, 47, 48, 49 For the most part, these reports have demonstrated an approximately equal frequency of MGMT promoter methylation between the younger and older populations, as well as a differential response to temolozomide and improved outcomes
Conclusions
The oncologic management of elderly patients is a topic of increasing importance. As is the case of GBM, cancer incidence increases with age. Because of the demographic shift of the general population, GBM is becoming a disease of the elderly. This is challenging for several reasons: advancing age is a poor prognostic factor, the disease biology is particularly aggressive, and treatment may be less effective and more toxic compared with a younger cohort. Population data have suggested that
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The authors declare no conflicts of interest.