Combined radiotherapy and chemotherapy
The result of the meta-analysis published in the British Medical Journal15 in 1995, which revealed a 13% reduction in risk of death associated with the use of platinum-based chemotherapy in combination with radical radiotherapy, is well known, but several points are worth reiterating. The first is that in most of the studies, the chemotherapy was given before radiotherapy, so the result does not reflect the potential benefit of concomitant radiotherapy and chemotherapy. Second, the benefit was not confined to patients with stage III disease, but was also observed in stage I and II patients, although because of smaller numbers the effect was not statistically significant.
There are good theoretical reasons why concomitant radiotherapy and platinum-based chemotherapy should be more effective than the two treatments given sequentially. There are at least three randomised trials which have confirmed an advantage for the concomitant versus sequential approach16-18, and the use of both treatments together should now be regarded as the standard of care.
Overall treatment time - CHART
The idea that some cancers repopulate at an accelerated rate during radiotherapy was first proposed by Withers19, and it is now widely accepted that to avoid this potential cause of treatment failure, overall treatment times should be kept short. This may be one reason why concomitant chemoradiation has proven more effective than sequential treatment. In a landmark study, Saunders and colleagues demonstrated that by giving a course of radiotherapy over 12 days instead of 42, local control could be improved, which in turn translated into a statistically significant survival advantage20. The acronym given to the regimen developed by Saunders was CHART (continuous hyperfractionated accelerated radiotherapy), but in order to complete treatment in such a short time, it was necessary to treat patients three times a day, seven days a week. This has proven almost impossible to implement in practice, and as we have demonstrated, similar benefits might be achievable with chemoradiotherapy, without the inconvenience of CHART21. Nevertheless, the results of the CHART trial have confirmed that it is possible to prolong survival with a non-surgical treatment, and that this is a result of improved local control, an observation that proved so elusive to the early investigators.
Radiotherapy for non-small cell lung cancer in Australia in 2002
The remarkable advances that have occurred in the last decade in the radiotherapeutic management of non-small cell lung cancer give cause for more optimism than was the case in 1992, but significant problems remain. We can deliver treatment with much more precision than ever before, but this requires accurate delineation of the target. In our own department, we have shown significant variation in tumour volume delineation by different radiation oncologists22 – we do not know how much of a problem this is in other departments, and whether it is associated with a risk of geographic miss. What account is taken during the planning procedure of tumour movement during the respiratory and cardiac cycles – the so-called 4th dimension?
We now have a much stronger evidence base on which to make recommendations to our patients about the most effective treatment, but will our resources allow us to implement best evidence? At a joint meeting of the Medical Oncology Group of Australia and the Faculty of Radiation Oncology, held in the Barossa Valley in August 2002, the participants were asked how they would manage a hypothetical case of inoperable non-small cell lung cancer. The majority recommended a combination of chemotherapy and radiotherapy, with 30 opting for induction, rather than concomitant chemotherapy, even though the available evidence favours the concomitant approach. Of the 30, only two stated they would recommend that approach by choice, the remainder indicated that it was a strategy forced on them by the long waiting times for radiotherapy. It is to be hoped that as the next decade evolves, the acquisition of new evidence for the best management of lung cancer will be matched by our ability to deliver it.
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