Chemotherapy and radiotherapy in advanced local non-small cell lung cancer
Dr Dirk De Ruysscher – University of Leuven, Netherlands
Can you tell us about your presentation?
This afternoon I’m going to give an overview about the combination of chemo and radiotherapy in advanced, locally advanced, non-small cell lung cancer because basically there are a lot of questions about what is the best radiotherapy, what is the best chemotherapy and how to combine them together. We all know that concurrent chemoradiation is better than sequential chemoradiation but the question still remains, is this for all patients the case? Certainly not, because some patients are too frail, too old or have other comorbidities and they can’t bear the concurrent chemoradiation which is much more toxic. The other problem is, of course, which chemotherapy can be combined safely with radiation and which radiation should be given? And that overview I will give this afternoon.
Are there studies underway to look at these issues?
Yes indeed. There have been studies in the past, of course, and there have been studies going on throughout the world, most of the time in Europe and the United States, covering this topic. Basically, we can identify what we can do at this moment and I will give an overview about the standard of treatment, that is to say the cisplatin etoposide or cisplatin vinorelbine together with the concurrent chest irradiation to a dose of 60-66Gy. But I will also discuss what are the topics for the future, like acceleration, does it mean something in this setting or not? I will also discuss the failure, so to say, of the large RTOG study from the United States where 60Gy was compared with 74Gy in a long overall treatment time and apparently in the first analysis the patients receiving the higher dose of radiation have a worse survival. Then, of course, this is preliminary but still we will discuss also what are the causes and what can be done? How should we interpret these results?
What can we do?
First of all I think it’s preliminary and I think also we should stress, we should congratulate the Americans that they have done this very large and very well done, well performed, study. First of all it’s preliminary but on the other hand it may also be the case that by delivering the radiation in a very long overall treatment time, that is to say 74Gy delivered in something like nearly eight weeks, may be simply too long, that’s a possibility. And maybe this high dose may be too toxic when delivered in this way, so with the technique that has been used in the RTOG study. Because in the sequential chemoradiation it is now clear that it is better to reduce the overall treatment time of the radiation because we know, and this has been published last month in the Journal of Clinical Oncology, that the overall survival, even after five years, is better when you deliver the same dose of radiation in a short overall treatment time. Of course, the question remains is this still true in concurrent chemoradiation when you combine radiotherapy with, most of the time, cisplatin etoposide or, in North America, with carboplatin and paclitaxel while you then give a higher dose but in a prolonged overall treatment time and maybe this is not beneficial and maybe we should go for an overall treatment time which is stopped at a certain moment so that we don’t prolong it too long because then cancer cells may accelerate their growth. On the other hand, it may also be that if you deliver such high doses that indeed toxicity may be an issue and also in the RTOG I think it was a very nicely done study but it was designed something like ten years ago and of course we know now better how to delineate abnormal structures and so on, thus avoiding more toxicity.
What’s next for these studies?
Both in Europe and in the United States there are a number of studies going on but in general, not all studies but in general, the main stream is to individualise the treatment so that means that we don’t deliver the same radiation dose to each individual; we will individualise more to lower the toxicity and also to increase the biological efficacy. What we also do, we deliver the radiation in quite a short overall treatment time or that’s not too long, not more than six or seven weeks, so that you can do it by twice daily irradiation in some studies or by giving a larger dose per fraction, that’s also a possibility. On the other hand, we take much more emphasis on the anatomical delineation of the normal tissues and to take into account much better than in the past the organs at risk, to avoid toxicity. I think the take home message that I will give this afternoon is that radiation dose intensification is not that, not at all, that is really a vital part of radiation research on both sides of the Atlantic, never mind the RTOG study because this is a totally different aspect because it was in a long overall treatment time. Outside of clinical trials I would really urge the people to use only the published fractionation and the published combinations between chemotherapy and radiation and don’t do something funny, we say, “Well it should work,” but you’re not sure without having done the proper prospective randomised trials.
