Primary Cerebral Malignancy – Treating Malignant Brain Tumors in the Elderly Population

Gadolinium-enhanced T2-weighted axial MRI images demonstrating the butterfly wing enhancement pattern and ependymal spread.

The following case presentation is intended to assess current practice habits for common neurosurgical challenges when class I evidence is not available.

THE CASE

A 78-year-old man with Type II diabetes, hypertension and a several-week history of progressive confusion was brought to the emergency room. His confusion was noticed by the home care nurse attending to his self-administered peritoneal dialysis for chronic renal failure. He denied headache but was clearly disorientated to time and place with severe short-term memory impairment. Family members commented that this represented a major change compared to his condition just a month ago. In addition, his neurological examination also demonstrated blunted affect, and he only could engage in superficial conversation. There were no other neurological findings.

He previously operated his own business from his home, where he lived alone. However, he could no longer look after his business or his day-to-day affairs. On the hospital ward he was able to feed himself, but his gait was unsteady and he fell and lacerated his forehead. He was given a score of 50 (requires considerable assistance with daily activities) on the Karnofsky Performance Scale, although because he required dialysis this was adjusted to a Karnofsky score of 40 (disabled and requires special care and assistance).

Laboratory investigations revealed no metabolic causes for his deterioration. An MRI scan with contrast demonstrated a bifrontal enhancing lesion with extensive involvement of the corpus callosum. These images also identified areas of apparent necrosis and ependymal spread. Very little edema was demonstrated on the T2-weighted images.

Considerations
The apparent undertreatment of malignant brain tumors in the elderly population is an area of debate (1, 3), especially with more effective and better-tolerated chemotherapeutic agents (9) and alternative hypofractionated radiotherapeutic courses available (4). Poor KPS status has been validated as a negative prognostic factor (6). Advanced age, decreased extent of surgical resection (7), and certain tumor haracteristics such as large size, eloquent location (8), necrosis, the type of enhancement pattern (7) and methylation status of the promoter of the MGMT gene (5) are additional variables that may modify outcome. It is, however, unreasonable to exclude patients from aggressive multimodal therapy purely on the basis of chronological age.

There are a number of factors that may explain why more than 20 percent of elderly patients with malignant gliomas are not treated more aggressively (2). In an elderly patient with neurological and or cognitive compromise, treatment may offer the prospect of prolonging survival or significant symptom relief for perhaps only a few months. In worse-case scenarios, there may be no symptom relief offered by treatment. This may not be sufficient motivation to a patient approaching the end of his or her life or for a neurosurgeon caring for this patient to opt for what may be perceived as aggressive therapy. Despite recent advances, it remains a challenge to provide responsible guidance to individual patients whose functional status and quality of life are poor. Clearly, the wishes of the patient and family are important determinants in the decision-making.

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Jacob Alant, MD, is a clinical fellow, and Rajiv Midha, MD, is professor and deputy head of the Department of Clinical Neurosciences at the University of Calgary in Canada. The authors reported no conflicts for disclosure. Send case presentation ideas for Gray Matters to Dr. Midha at [email protected].

References

1. Barnholtz-Sloan JS, Williams VL, Maldonado JL, Shahani D, Stockwell HG, Chamberlain M, et al: Patterns of care and outcomes among elderly individuals with primary malignant astrocytoma. J Neurosurg 108:642-648, 2008
   
2. Bussiere M, Hopman W, Day A, Pombo AP, Neves T, Espinosa F: Indicators of functional status for primary malignant brain tumour patients. Can J Neurol Sci 32:50-56, 2005
   
3. Chiocca EA: Being old is no fun: treatment of glioblastoma multiforme in the elderly. J Neurosurg 108:639-640, 2008
   
4. Chang EL, Yi W, Allen PK, Levin VA, Sawaya RE, Maor MH: Hypofractionated radiotherapy for elderly or younger low-performance status glioblastoma patients: outcome and prognostic factors. Int J Radiat Oncol Biol Phys, 56:519-528, 2003
   
5. Krex D, Klink B, Hartmann C, von Deimling A, Pietsch T, Simon M, et al: Long-term survival with glioblastoma multiforme. Brain 130:2596-2606, 2007
   
6. 6. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, et al: A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95(2):190-198, 2001
   
7. Sanai N, Berger MS: Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753-764, 2008
   
8. Stelzer KJ, Sauve KI, Spence AM, Griffin TW, Berger MS: Corpus callosum involvement as a prognostic factor for patients with high-grade astrocytoma. Int J Radiat Oncol Biol Phys 38:27-30, 1997
   
9. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987-96, 2005

Responses: Idiopathic or Aneurysmal Hemorrhage? This case was published in the AANS Neurosurgeon 17(2):44-45, 2008. Click here to review the case. THE CASE Angiogram-Negative Subarachnoid Hemorrhage: Idiopathic or Aneurysmal Hemorrhage? Survey Results Summary Virtually all of the respondents (95 percent) recommended that further investigation was required to determine a potential underlying anatomical lesion that would explain this patient’s subarachnoid hemorrhage. Greater than three quarters of the respondents favored repeating a vascular imaging study, with approximately half choosing the more invasive catheter angiogram, while one quarter felt that a CT angiogram was sufficient. MRI of the cervical spine was suggested by just greater than 15 percent of those responding, while a single respondent said an MRI study of the brain was indicated. There was a range of opinion about when the imaging study should be carried out, but a clear majority favored a relatively early study. While 30 percent would do the study in one to two days, most (just less than half) would order the repeat study to be performed in one to two weeks. For those suggesting a study at three weeks or longer, a wait of more than six weeks was the preference. Case Commentary The CT appearance of perimesencephalic subarachnoid hemorrhage is more commonly an isolated and localized area of hemorrhage anterior to the upper brain stem. In that setting, I am more comfortable in making this diagnosis, and if a catheter angiogram is negative and there is no vasospasm, I do not routinely restudy the patient. I will do a C-spine MRI to rule out the rare upper cervical arteriovenous malformation. In the case presented here, the large amount and diffuse distribution of subarachnoid blood would lead me to obtain an arteriogram again in one to two weeks even if the first study were negative. If the second study also were negative, I would not do a third. I am not comfortable enough with MR angiography or CT angiography to consider either definitive if negative in a CT-documented subarachnoid hemorrhage and still rely on a catheter study. Steven J. Barrer, MD, Abington, Pa.

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