Primary Brain Tumours in the Elderly
Tara Morrison, MD and James R. Perry, MD, Crolla Family Brain Tumour Research Unit, Division of Neurology, Sunnybrook and Women's College Health Sciences Centre; University of Toronto, Toronto, ON.
Primary brain tumours are most commonly diagnosed in elderly individuals and the incidence of these uniformly fatal malignancies is on the rise. Recent studies have shown that the most common of these tumours, the glioblastoma multiforme, is genetically different in elderly compared to younger patients. Current research studies exploiting the genetic differences of these tumours as anti-cancer targets hold promise for the immediate future. At present the focus of brain tumour treatment is excellent supportive care. Radiation treatment and chemotherapy are being actively revisited to maximize quality of life. In addition, complications such as venous thromboembolism, seizures and therapy-induced adverse effects have received much attention and are reviewed in this article.
Key words: brain neoplasms, glioblastoma multiforme, palliative care, chemotherapy.
Introduction
Primary brain tumours represent a small portion of the total primary cancers diagnosed each year in Canada, with an annual incidence of 2,400 cases and over 1,500 deaths.1 A number of sources indicate this incidence is rising, especially in elderly populations.2,3 The current trend of an aging population suggests the incidence of new primary brain tumours may continue to rise. Malignant gliomas are the most common primary brain tumours and, despite therapy, their prognosis is extremely poor. The elderly benefit less than younger patients from therapy, and are less likely to be offered treatment.4 In this article, we summarise the key issues in management of primary malignant brain tumours in an elderly population, and the dilemmas for the future. Although we do not discuss metastatic brain tumours or benign tumours such as meningiomas, many of the supportive care principles discussed here can be generalised to these patients as well.
Brain Tumour Classification
It is likely that brain metastases are slightly more common than primary brain tumours. Of the primary brain tumours, the most frequent are the gliomas--derived from the supporting cells of the brain, or "glia". The most abundant glial cell type is the astrocyte, and tumours derived from astrocytes are called astrocytomas.5 Table 1 presents a more detailed description of brain tumour classification. The most frequent primary brain tumour is the grade IV astrocytoma, also known as the glioblastoma multiforme (GBM).
Primary vs. Secondary Glioblastoma Multiforme
The evidence suggests that GBMs in older patients are more likely to arise de novo (primary GBM), while those of younger individuals tend to arise from the progression of a lower grade glioma (secondary GBM). The molecular genetics of primary versus secondary glioblastoma are quite different, suggesting that this tumour may represent at least two different diseases with identical histopathology (Figure).6
What is "Elderly"?
Difficulties exist in any discussion of issues affecting older patients. At what age does a person become elderly? Is it purely a function of age that can be set at an arbitrary number, such as Old Age Security at age 65? Or should we consider tumour biology in the definition? There is a very distinct survival advantage for patients younger than 45 years with GBM. Few oncologists would consider a 52-year-old truly the same as an 80-year-old, though their survival curves are, on average, nearly identical. This may reflect the different genetic origins and biologies of primary and secondary glioblastomas.
Therapies
Surgery
All studies of surgery versus biopsy have been retrospective to date, and it is unlikely that there will ever be a randomised controlled trial of these issues. Kelly and