DR. BRENNAN: Questions and comments? Clearly, with the tissue before and after, it offers an extraordinary opportunity to look at the radiobiology. Other questions?

DR. NIELSEN: You know, the intensity modulated radiotherapy has been discussed in many side groups and in many different societies. I think, looking at what is up there, it is obvious. On the other hand, you always wonder how you will be able, in a reasonable number of patients, to show the advantage of the IMRT as you demonstrate there. So, my question would be, how many patients do you think you actually need for doing what is up there?

DR. BELL: What we thought about in terms of the target for that phase III study -- to get into a discussion of the actual trial design -- might be, for example, to look at reduction of complications following neoadjuvant radiotherapy.

As an example, some groups -- Mass General, M. D. Anderson has identified a 35 percent risk of complications following neoadjuvant radiotherapy. That would be a good target for seeing if IMRT would reduce that complication risk.

DR. BRENNAN: Ole, I don't mean to be unfair. I think the organizations are rather keen that we don't define for you a clearly defined trial. We define principles that you could accept which would move the field ahead.

DR. NIELSEN: Then you misunderstood what I said. I am not against what is up there. I am for it. I am just, as a footnote, saying that in other side groups where discussions are ongoing, where they go in reality to make the trial they have realized that there may be some problems designing it. That is just what I am saying.

DR. BRENNAN: Unfortunately, we are all too acutely aware of that. Other questions or comments for Bob?

DR. O'SULLIVAN: Bob, thanks very much for outlining our discussion yesterday. I think one of the big problems, which gets back a little bit to what Ole just said, is that we have to still learn how to do this treatment.

It is not even a question of piloting. It is even more fledgling than that. We have to determine issues such as proper immobilization, recognizing that the means of immobilization can actually interfere with the intensity-modulated beams.

For example, we are looking at various forms of surface optical tracking of the limb to make sure it stays immobilized, rather than using the traditional types of physical devices that would, in fact, regrettably interfere totally with the whole objective of IMRT, which is to spare the tissue.

So there is a lot of primary work that needs to take place for very physical reasons to be able to deliver this treatment in the kind of accurate way that is required. We run this great danger of actually missing the area that we are most concerned about, which I think has to be overcome. Then there is also the multidisciplinary interaction in terms of what, in fact, is the target. Are you going to deal with the fascia? Do we deal with the fascia? Do we deal with the area where the biopsy was done, et cetera, et cetera. So, all of that has to be worked out.

I think it is a great challenge, and I think we are going to do it, but I think we have to be careful and do it very methodically and with all these issues in hand.

DR. BELL: I think the risk of not doing it in this fashion, the risk of us not grabbing this opportunity and making it go forward is that it is going to be done in haphazard fashion and the management of soft tissue sarcoma in the extremity may take a step backwards. We may see increases in local failures because of inadequate treatment of tumor, because of the lack of principles we just enunciated.

DR. BRENNAN: For those of you who don't deal with this problem -- at the risk of being sexist, I would ask Dr. O'Sullivan to show you his video MRI, spread over an hour, of the prostate.

The men in the room will not appreciate the amount of movement that takes place in the prostate under even normal circumstances under the MRI. It is quite a frightening event; but he will show it to you.

DR. O'SULLIVAN: I can show it on a PowerPoint afterwards. It is interesting. It is a way of imaging the target to see what degree of movement is possible. You obviously can't do it with CT because you are exposing someone to radiation for an hour; but you can do it with MRI, and we can take videos of MRI and show the movement, which is what Murray is referring to. That is, again, something I think we should be looking at, if we are getting at this type of precision of coverage of the target.

DR. BRENNAN: I think the more that we can, from this group, encourage that other diagnostic modalities be included in moving this field ahead. We have focused very much on the tissue; but the whole concept of moving imaging modalities ahead, which we really haven't discussed, is a very important one. Whether it is imaging for localization, whether it is PET scan for advanced disease -- we really haven't addressed that. It is purely a matter of time.

DR. DEMETRI: I wanted to say exactly the same thing. Just replace IMRT with a new drug and you have the issue that we are talking about.

I don't want to focus on the specifics here, but I think it is great to have this group of radiation docs, medical docs, surgical docs, all talking about what are the questions we want to ask in this field. Here is a new technology. How is the field going to test it in sarcomas, and really capitalize on that? So, rather than focus on the specifics, I am encouraged by the give and take, the back and forth, about wanting to take a technology that we all see going out there haphazardly, as Bob said, and saying, "Look, it is important enough, we use radiation, and we, as a field, should capitalize on it," and then let the experts decide how to test that in our field.

I like the fact that you brought that up. I then encourage us to then help develop the multidisciplinary strategy that will help us develop the specific questions in light of these specific limitations that Brian is talking about.

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