Modern radiotherapy can give good quality survival for six months

Editor–We wish to correct misinformation reported by Elizabeth Davies and colleagues in their study of survival after radiotherapy for malignant cerebral glioma.1 Contrary to their suggestion in the acknowledgements, the study had not been supported by the Medical Research Council Brain Tumour Working Party. As the poor study design indicates, the study had never been officially submitted to the Medical Research Council and had therefore not been subjected to its rigorous protocol review process. For example, Davies and colleagues report that their criteria for assessment of treatment toxicity were derived in a “pragmatic fashion after discussion” by a “process of elimination,” without evidence from imaging to exclude tumour progression. This would be totally unacceptable, let alone publishable. The impression that the 105 patients represent an unselected consecutive series is difficult to believe as the seven centres should, over two years, have seen 400-800 eligible patients.2

The reported adverse prognostic factors in patients with high grade glioma have been known for over 18 years.3 Although the authors appropriately conclude that severely disabled patients have a poor prognosis and may not be suitable for active treatment, the fact that they were considered for intensive treatment at all is surprising. Centres specialised in the treatment of patients with brain tumours would not have accepted patients with such a poor prognosis for high dose radiotherapy. Most of the patients also seemed to receive initial whole brain radiotherapy followed by a radiation boost to the tumour. Whole brain radiotherapy is nothing but toxic and has not been practised in specialist centres for many years.

Given the use of outdated and often inappropriate high dose, wide field radiotherapy and the flawed assessment of morbidity from treatment, the conclusion that radiation is of little value and simply results in adverse effects seems ill advised. High grade gliomas are among the most devastating of malignancies, with few useful treatment options. Modern radiotherapy, although not curative, offers a survival benefit of about six months,3 and for most patients without functional impairment the quality of survival is good. Without comparative data on the quality of life, how can we decide whether prolongation of survival by six months with clinical deterioration in a small proportion of patients is worse than the alternative of progressive functional decline, which happens in all patients without treatment? Yes, we do need more effective treatments without morbidity, but to throw out a proved treatment on the basis of misinformation is a travesty to evidence based medicine, to which the BMJ claims allegiance.

Patients should be treated in specialist units

Editor–Conducting in depth interviews using a non-validated subjective rating scale in a selected group of patients with incurable malignancy who are receiving intensive palliative treatment is likely to yield a description of misery experienced by patients and families. Targeting patients treated outside cohesive specialist oncology units with defined information policies and support systems will highlight a range of dissatisfaction and misinformation. Elizabeth Davies and colleagues studied patients with high grade glioma from centres without dedicated neuro-oncology units,1 and their results provide a good argument for a reorganisation of cancer services to improve cancer care, in which specialist units provide not only state of the art treatment but also, and more importantly, a package of care and support.

The treatment of patients with high grade glioma within our neuro-oncology unit, which Davies and colleagues chose not to examine, has long recognised all the problems highlighted in their article.1 Care and support are provided by a team headed by a neuro-oncology nurse specialist; in depth interviews with patients and their carers provide oral and written information and the opportunity to return for further interview. The isolation of patients and their families has long been recognised with the formation of relative as well as patient support groups. The severe tiredness experienced by patients after treatment, largely as part of the somnolence syndrome, has also been acknowledged, and specific support is provided by a nurse led telephone follow up system when symptoms are at their worst.2 The need for subsequent support and care is organised through early referral to palliative care services and less reliance on hospital and doctor based follow up, which is being largely replaced by nurse led telephone follow up and free access to clinics and to medical and nursing staff.3

Patients with high grade glioma represent a group of patients with incurable malignancy suitable for palliative intervention, and the distressing nature of the range of neuropsychological impairment means that patients and families should be given particular sensitivity and support, which is not necessarily measured in financial terms and in any case is not costly. The summary of interviews gives a glimpse of the range of problems and misery that can to some extent be alleviated by an organised system of care and support.1 Davies and colleagues provide us with an excellent argument for this group of patients to be treated in cancer centres with specialist units, where such support services are available.

A relative's perspective

Editor–My late husband was interviewed by Elizabeth Davies and colleagues1 2 and certainly experienced adverse effects after radiotherapy in the treatment of malignant cerebral glioma. No doubt the degree to which this can be seriously debilitating depends somewhat on the particular part of the brain that has been subjected to radiation. Although my husband did suffer some neurodeficit, we were blessed in there being no personality changes and grateful for some extension of life; others may be less fortunate and hold a different view.

Editor's Choice asks: “So is the treatment worth it? Only the patients and their relatives can decide.”3 The medical profession will weigh up the costs, and our perspectives may well vary. For my husband and me each extra day that this treatment gave was valued without question. The disease was a shock and so unforeseen that any further time allowed a chance. For what? Mainly, to prepare for the changes that death brings but also to share some gracious times together in some real depth.

The tiredness afflicting many patients after radiotherapy is not like the common tiredness resulting from daily undertakings. It is a heavy pall on the being, a “twilight zone” which lessens its grip in stages. Its possible duration should not be underestimated, and the single kindest gesture to patients and families is to give adequate warning of this. Depression follows easily if a patient fails to feel some expected improvement: “I must be getting worse” is the natural response.

The extension of such life as can be provided is a balance between hope and emotional acceptance which eases, for most, the current inevitable outcome. It is palliative to the inner being of all those involved even if the body's stay is not assured. Who knows the real value at such times? Nevertheless, to witness the indiscriminate devastation of radiotherapy on such a fine mechanism as the brain leads one to question its continuing use as the most appropriate treatment. Will research come up with some more subtle answer in due course?

Patients' awareness of prognosis may be confounded by successful coping mechanisms

Editor–In their interview study of patients with malignant cerebral glioma Elizabeth Davies and colleagues found that only a quarter (19/75) were fully aware of their prognosis.1 This result is not in line with our findings from a recent, similar study.2 As 11 of the 19 patients whom we could evaluate (not 30 as incorrectly stated by Davies and colleagues) spontaneously associated their disease with death–typically stating: “I hope I'll get another two years”–we concluded that most patients seemed to be aware of the gravity of their situation.

This discrepancy in found awareness may be attributable to different interpretation criteria. Patients who conveyed some fear of dying but also that they had some reasonable chance of being cured were classed by Davies and colleagues as being partly aware. This may be correct. It may also indicate, however, that these patients were quite aware of the severity of their situation but at the same time were dealing with the psychological threat.2 This phenomenon is known as middle knowledge: patients are aware but seem to be unaware at the same time.3

For example, one of us (PS) recently talked with a man with widespread cancer. In contrast to his behaviour in earlier encounters he made no attempt to raise himself from his wheelchair. PS commented on this, and he replied forcefully: “Of course I can't walk any longer! If you don't eat porridge in the mornings you don't get enough energy. Yesterday I ate none, but this morning I was actually able to eat a couple of spoonfuls, so I think it's getting better.” Later, during the same conversation, PS asked him about the outcome of the x ray examination he had undergone two days earlier. He replied more laconically: “It detected metastases all over the skeleton.”

This type of contradiction is everyday clinical reality. We think that this patient was aware of his grave situation, but his awareness was dissociated from its personal impact. The patient perceived correctly, but the perception was disavowed of its meaning.4 By this mental manoeuvre he created hope.2 If this patient was included in a study would he be regarded as fully or partly aware? If he were considered to be fully aware his awareness might be overestimated. But if he were considered to be partly aware the risk of underestimating his awareness might be even greater, his awareness being confounded with processes aimed at psychological survival. In other words, instead of estimating awareness we may in fact be estimating the extent of successful coping.

It is up to all of us to sharpen our reflections and definitions on this issue.

Modern radiotherapy techniques are needed to spare normal brain tissue

Editor–The two papers by Elizabeth Davies and colleagues highlight the distressing aspects of malignant gliomas,1 2 including the difficulties faced by clinicians trying to balance the increased survival benefit from a higher radiation dose3 against morbidity related to treatment. For radiotherapists managing treatment in these patients the first paper adds considerable weight to the argument for using modern radiotherapy techniques to spare normal brain tissue.

This study confirms the view that radiotherapy generally prolongs survival but does not necessarily improve the patient's functional and neurological state.1 Deterioration occurred in 27% of patients, just as in the Medical Research Council study evaluating radiotherapy doses.3 In most patients the initial phase of treatment used large parallel opposed fields up to a dose of 40 Gy, and this was followed by a smaller volume boost, but these details are not complete.4 A better approach is to treat the tumour with an appropriate margin, as imaged by computed tomography. This is equally effective in terms of tumour control and should now be regarded as standard treatment. Although we agree with the general conclusions of Davies and colleagues that the incidence of deterioration relates to higher dose and volume of brain irradiated, this is not a new concept. Dose-volume effects for late radiotherapy changes in the central nervous system are well recognised, ranging from necrosis to subtle neuropsychometric impairment.5

The second paper of Davies and colleagues tries to describe the balance of quality and quantity in the survival of patients with glioma, and they highlight the distress experienced by patients and relatives.2 Despite the comparatively poor outcome in terms of survival and function, few patients regretted having radiotherapy, and the potential benefit of treatment to fit young patients whose survival was 40% at two years was understated.1 The effect of being unable to drive was not assessed. This may have a profound effect on daily living and is a feature of the condition, not the treatment. Patients in the study were often unaware of the full significance of their prognosis. The authors concluded that this was largely because the professional or relative was protecting the patient from distressing information. However, patients can choose what information they want. Although patients with severe confusion were excluded, more subtle impairment of cognitive function often confounds detailed discussion.

We agree with the key messages, especially that techniques sparing normal brain tissue from radiation should be considered.1 It is time for the NHS to acknowledge the need to provide modern radiotherapy technology to achieve this objective.

Authors' reply

Editor–The past chairman of the Medical Research Council Brain Tumour Working Party gave his initial support to our study, and the working party allowed us to include 25 patients who were recruited to the council's trial of adjuvant chemotherapy. We believe it to be usual to thank colleagues for help, without implying their approval of the study design, results, or conclusions.

The Medical Research Council Brain Tumour Working Party describes our study design, reviewed and supported by the Cancer Research Campaign, as poor. The working party shows an unusually narrow view of scientific activity, not understanding how to address research questions outside a trial design or the need to study patient outcome in everyday practice. Trials showing that radiotherapy prolongs survival by six months failed to assess quality of life,1 leaving a legacy of doubt and disagreement about best practice.2 Our study aimed to address these doubts by describing the quality of life and effects of radiotherapy in patients treated at six well respected London hospitals that provide neurosurgical and radiotherapy services to most of the North Thames region.

The working party asserts that we recruited too small a proportion of eligible patients when, in fact, we made it clear that centres were included in a stepwise fashion over two years. Only at the end of the study were we recruiting from all six centres. The working party also raises the issue of selection. We can state confidently that we made no selections from the patients about whom we were informed. There is, of course, always the possibility that we were not offered patients for recruitment to the study. Even randomised trials succeed in recruiting only a proportion of those eligible. However, the survival curve for our patients is so similar to those previously published that we believe we have recruited a representative sample of patients with malignant glioma.

For the working party to imply that our findings are irrelevant because “whole brain radiotherapy…has not been practised in specialist centres for many years” shows a surprising lack of awareness of what is happening in other treatment centres. The group criticises the absence of imaging evidence to exclude tumour progression in our assessment of adverse effects, although early delayed reactions to radiotherapy are indistinguishable from tumour recurrence on imaging.3 We make no apologies for the clinical evaluation, in association with a radiotherapist, of deterioration, and we have made clear the logic–patients whose condition improves or who survive for six months are unlikely to be experiencing tumour recurrence.

Douglas Guerrero and colleagues say that our interview method used a “non-validated subjective rating scale.” Semistructured interviews that follow developmental work and pay attention to interrater reliability are used widely in disciplines other than medicine.4 How, other than by listening to patients and relatives, is it possible to represent the kinds of experience and reflections described by Julia Chappell?

We regret misquoting the denominator in the study by PÄr Salander and colleagues. Their results and ours underline the complexities of understanding patients' and relatives' ways of coping with threatening information.

Finally, Guerrero and colleagues criticise us for choosing not to study patients from their specialist neuro-oncology centre at the Royal Marsden NHS Trust. We must remind Michael Brada, the head of the centre and one of Guerrero's colleagues, that it was his written preference, and not ours, that the centre's patients were not included. We do, however, support the view that care should be better integrated. We have convened a multidisciplinary working group to develop evidence based clinical guidelines for practice covering many psychosocial aspects of care.5 Recognising that research findings may not immediately translate into everyday practice is the first step in improving the quality of care for all patients. All of us concerned in the management of patients with malignant glioma are determined to do this.