Treatment > Radiotherapy

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Radiotherapy for malignant glioma

Anna Gregor, Ann Cull

ICRF senior lecturer in clinical oncology University of Edinburgh, Edinburgh EH4 2XU. Consultant clinical psychologist ICRF Medical Oncology Unit, Western General Hospital Edinburgh EH4 2XU

Quality as well as quantity of life is important and must be formally assessed

The management of malignant glioma presents challenges for neurosurgeons and oncologists alike. Surgery with postoperative radiotherapy remains the "gold standard" treatment for this group of patients. Neurosurgical procedures are essential for accurate diagnosis, and surgical decompression relieves raised intracranial pressure and improves neurological deficits. Despite optimal surgical resection, half of patients die within three months of the operation. Postoperative radiotherapy increases median survival to between nine and 12 months, but, by two years, 90% of patients are dead.¹ Adjuvant chemotherapy provides a small survival advantage at one year, but this disappears by two years.

Well conducted clinical trials provide convincing evidence that patients' age, histology (anaplastic astrocytoma or glioblastoma multiforme), and degree of functional impairment wrongly influence the duration of survival.² They offer a rational basis for selecting treatment for individual patients. Disabled patients with glioblastoma multiforme aged 60 years or over will derive limited benefit from aggressive treatment.³ Conversely a 35 year old patient with post-resection histology of anaplastic astrocytoma and minimal neurological deficit has a high probability of remaining well for 18 months or longer if treated with the optimal schedule of high dose radiotherapy. In both of these scenarios it is important to ensure that the toxicity of treatment does not outweigh the survival benefit.

The effect of radiation on the brain has a classic time dependent course, with severity related to total radiation dose, individual fraction size, and the volume of brain irradiated.⁴ Any evaluation of toxicity must therefore take these variables into account. The acute effects of clinical radiation schedules have often been underestimated and thought to be limited to alopecia. However, prolonged tiredness and temporary functional deterioration due to delayed postradiation reactions are well recognised. These are disturbing to patients and may confuse their clinicians unless both are aware of the possibility.

Studies of functional impairment and the formal evaluation of the impact of tumour and treatment on patients' quality of life have modified paediatric neuro-oncology practice and contributed greatly to the understanding of radiation toxicity.⁵ However, such information has been lacking in adult patients.⁶ Self reported data from patients have repeatedly been found to give an unreliable index of mental impairment, and standardised neuropsychometric testing remains the method of choice for assessing cognitive function.⁷ Such tests are time consuming and require the input of staff trained in neuropsychology to interpret them.

Patients may be unable to complete questionnaires

Reliable and valid questionnaires are available for assessing other dimensions of the quality of life of patients with brain tumours. Osoba and colleagues have developed a 20 item module⁸ to complement the well established core quality of life questionnaire, the European Organisation for Research into Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30).⁹ This brain cancer module has satisfactory psychometric properties, including responsiveness to differences in patients' neurological status. While its motor dysfunction scale correlates highly with recognised scales of performance it covers a broader range of functions and problems (including communication deficit, visual disorder, and future uncertainty).

In longitudinal studies of patients with brain tumours, deteriorating neurological status can render surviving patients unable or unwilling to complete questionnaires. However, there is now evidence that ratings of quality of life from doctors and informal care givers can be useful. In a formal comparison of ratings by patients, care givers, and doctors, doctors were better at detecting change in physical function than patients and less good at assessing change in pain or social function.¹⁰ In this study relatives' ratings were close to those of patients. However, agreement in ratings between proxies and patients is likely to be lower for more impaired patients,¹¹ particularly those who are confused. More studies are needed to examine the reliability and validity of patient and proxy responses.

Symptoms are often underestimated

The two reports in this week's BMJ by Davies et al (pp 1507,1512) are welcome in highlighting the plight of patients with malignant glioma,^{12 13} but these descriptive reports of current practice from selected institutions illustrate some methodological problems that work of this kind is subject to¹⁴ and which limit the interpretation of their findings, for example the selection of consecutive patients from stepwise selected institutions may have introduced bias. Certainly, the choice of treatment for individual patients showed variation in both radiation technique and dose, and some patients also received chemotherapy. We do not know the basis for the choice of treatment schedules or important variables such as the dose of corticosteroids. Patients' deficits in language and cognition caused by the tumour may have impacted on their ability to participate in the interview. Some of the "tiredness" attributed to radiotherapy could have been the result of tumours affecting the frontal lobes. Radiation morbidity is defined using retrospective criteria, inviting radiotherapy opinion on selected evidence rather than performing an independent review. These interpretations may have been presented instead of the evidence because the data is difficult to summarise, but this represents a considerable investment in time for staff and patients and deserves to be formally reviewed.

What we have learnt is that patients with malignant glioma suffer from symptoms that are often underestimated and which may be related to radiation as well as the underlying tumour. In future formal comparisons of toxicity and quality of life must accompany evaluations of all "new" clinical interventions. The methodology is difficult and assessments are best anchored to randomised trials.

One such trial, of best supportive care with or without a short and simple course of radiotherapy, is about to be launched by Britain's Medical Research Council (BR09). Its primary endpoints are comparisons of survival, survival free from functional deterioration, and quality of life. These will be evaluated by the parallel administration of the EORTC QLQ- C30 and the brain module to both the patients and their proxies. This trial will define the role of radiotherapy in patients with poor prognosis. Strategies of more intensive treatment will soon be under investigation for those with better prognosis. All will have functional and quality of life endpoints.

Despite some new experimental approaches, radiotherapy remains the single most important treatment for this group of patients. Delivery of optimal radiotherapy schedules must be accompanied by emotional support and help with the physical disabilities faced by these patients and their carers. This holistic care is multifaceted and best delivered by a specialist neuro-oncology team, supported by appropriate investigative and paramedical infrastructure in the hospital and palliative care in the community. Audit of the outcome of the care provided by such teams should include measures of quality of life and patient satisfaction. At a time when reorganisation of the delivery of cancer care may bring benefit to patients with common cancers, the "Cinderella" patients with malignant glioma should not be left behind.

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13. Davies E, Clarke C, Hopkins A. Malignant cerebral glioma--II: Perspectives of patients and relatives on the value of radiotherapy. BMJ 1996;313:1512-6. [Abstract/Free Full Text]

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© 2004 BMJ Publishing Group Ltd