Management of High-Grade Gliomas in the Elderly

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The incidence of glioblastoma (GBM) has been increasing over the past several decades with majority of this increase occurring in patients older than 70 years. In spite of the growing body of evidence in this area, it is still unclear as to the optimal management of elderly patients with GBM. The elderly are a heterogeneous population with a range of comorbid conditions, and functional, cognitive, and physiological changes, and ideally treatment decisions should be made in the context of a comprehensive geriatric assessment. Patients with a poor performance status or assessed as “frail” might be considered for less aggressive therapy such as hypofractionated radiotherapy or single-agent temozolomide, whereas those with a good functional status may still benefit from maximum resection followed by combined radiation and chemotherapy. Recent randomized trials suggest molecular markers such as O6-methylguanine-DNA-methyltransferase promoter methylation testing could help guide these decisions, particularly when considering monotherapy with temozolomide vs radiotherapy. Ongoing studies seek to clarify the role of concurrent treatment in this population. Clinical judgment and discussion with patients and families, weighing all the options, are necessary in each case. Ultimately, patients and the neuro-oncology community should be encouraged to participate in clinical trials focused specifically on caring for the elderly patient with GBM.

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.

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