Management of Malignant Gliomas—Limited Benefit of Radiotherapy

ABSTRACTS & COMMENTARY
Sources: Davies E, et al. Malignant cerebral glioma-I: Survival, disability, and morbidity after radiotherapy. BMJ 1996;313:1507-1512; Davies E, et al. Malignant cerebral glioma-II: Perspectives of patients and relatives on the value of radiotherapy. BMJ 1996;313:1512-1516; Meckling S, et al. Malignant supratentorial glioma in the elderly: Is radiotherapy useful? Neurology 1996;47:901-905.

Two independent studies have recently examined the usefulness of radiotherapy in treating malignant cerebral glioma, assessing not only survival, but also measures of neurologic function. Davies et al performed a retrospective study of 105 tumor patients with a median age of 52 (range, 21-75) from seven centers in London (59 had biopsy, 46 partial resection, 92 received radiotherapy, and 13 steroids alone). The main outcome measures were survival, time free from disability, and changes in disability after treatment. The six- and 12-month survival rates for radiotherapy were 70% and 39%, respectively. However, most patients (68%) with an initially good clinical status experienced clinical deterioration and severe fatigue post-radiotherapy, and 17% had some permanent loss of function. These adverse effects correlated with the increased doses of radiotherapy. There was no functional benefit of radiotherapy for patients with lower clinical performance scores at the time of diagnosis. The authors conclude that more elderly (> 60 years) and severely disabled patients rarely gain neurologic benefit from radiotherapy, whereas even those with higher initial neurologic function can experience considerable adverse effects.

Meckling et al performed a retrospective analysis from a Canadian registry of all patients aged 70 and over presenting with malignant cerebral glioma (symptoms including dementia 50%, hemiparesis 41%, headache 35%, and seizures 21%). Multiple treatment factors in 103 patients were compared with survival and neurologic function scores. All patients died, with a median survival time of 3.9 months. Better neurologic function at diagnosis and administration of radiotherapy were independently associated with a slightly longer survival (P < 0.001) but only in patients less than 80 years of age. Importantly, neurologic status only rarely improved following radiotherapy.

COMMENTARY

The value of radiotherapy for elderly patients with malignant cerebral glioma, not only for survival, but for maintaining neurologic function, has been reasonably addressed in the above studies. This is an important question as the geriatric population increases along with the incidence of malignant cerebral gliomas. The management of this brain tumor presents challenges for the neurologist, neurosurgeon, and neurooncologist alike. Most patients will die within 3-4 months regardless of the course of treatment, such that quality-of-life measures should be a primary consideration. Earlier studies had shown that median survival after surgery for patients with steroids alone was only 14 weeks, compared to 38 weeks after radiotherapy (Walker MD, et al. J Neurosurg 1978;49:333-343). However, elderly patients were usually excluded from such randomized studies, which is important given that age apparently has a striking negative influence on survival.

The above analyses of the use of radiotherapy may be limited given the variation in surgery, radiation dose, technique, and the additional use of chemotherapy in a few patients. Nonetheless, it is reasonable to conclude that radiotherapy is generally not indicated for elderly patients, particularly those with lower neurologic function at the time of diagnosis. These studies may simply confirm many clinicians first-hand observations over the years. Given finite medical resources, and the disproportionate amount of medical care and expense in the terminal stages of life, these studies support the concept that certain treatment measures can be justifiably withheld in elderly patients with malignant cerebral glioma. We await systematic testing of newer technologies such as radiosurgical knives or radioactive implants in an older patient population, but, at present, conventional radiotherapy should be reserved for more intact younger patients. —ba