Clinical Applications of P.E.T. in Oncology

Speakers

• Dr Vanessa Bernstein: Medical Oncology, Vancouver Island Cancer Centre
• Dr Simon Sutcliffe: CEO, BC Cancer Agency
• Dr Peter Conti, MD: Associate Professor of Radiology, Clinical Pharmacy and Biomedical Engineering USC
• Dr Richard Wahl, MD: Director of Nuclear Medicine, John Hopkins University

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Dr Bernstein (part of main presentation):

So what should our BCCA practice guidelines be for PET?

• Funding for PET should be available for evaluating breasts that are difficult to examine by mammography or ultra-sound where there is clinical suspicion of disease.
• Funding should be available to evaluate patients for distant metastases if current imaging fails to identify disease and there is clinical suspicion or perhaps biochemical suspicion such as a rising tumour marker or increase liver enzymes suggest it.
• There should be funding to evaluate patients for response of therapy if it cannot be determined by other means and such knowledge would change patient management either by stopping them from receiving further toxic therapy, allowing more effective therapy to be started earlier or perhaps when patients have failed several therapies and are on to very expensive therapies; the PET scan might even be cheaper than giving them 3 of 4 courses of treatment to see if it is working.
• Finally the evaluation of internal mammary node and axillary nodes should only be done in the context of clinical trials. Thank you very much.

Dr Sutcliffe: OK. Lets take breast cancer now, obviously more controversial. I think we clearly heard: directive problem solving, which obviously is by individual indications. We heard evaluate breasts that are difficult to examine by mammography and ultra-sound, presumably where there is believed to be a serious risk of breast cancer, we heard the evaluation of distant metastasis where there is equivocation on other modalities. We heard evaluation of the response to therapy if it can’t be determined by other investigative means and we heard evaluation of IMC and axillary nodes, only in the context of further clinical research studies; I believe that is the correct interpretation. I think with the directed problem solving everyone could be quite comfortable with that as an indication, with respect to the others the dense breast difficult to determine but with a suspicion on breast cancer. Any comments with respect, from our expert faculty on that indication?

Dr Wahl: Well I guess that could open up a lot of patients to the study and I guess it depends on how much money you want to spend. I mean the number of women with difficult to evaluate breasts with risk, I mean I would suppose that anybody between 25 to 50 with like a mother with breast cancer with somewhat increased risk so. I would say, at least my own experience in PET in breast cancer would be these women’s breasts would be quite difficult to evaluate as they are younger, the background activity in normal breast is higher and if one looked at the evidence specifically for smaller lesion detection and try to segregate out women with radio dense breasts, I mean I think that you might start running out of evidence, in other words, I mean clearly smaller lesions you do have difficulty detecting, and I think smaller lesions with higher background activity are harder to detect so I personally think that you could open up a lot of issues. And then the other issue is if you did find something, there is the issue of how do you biopsy it, once you identify it, if it is not identified by other methods. Now this is an interesting challenge and I think a number of groups have spent time trying to develop methodologies for biopsying FDG or PET avid lesions. But exactly how to do it is still not routine. So you can say you can say that well you go and do an ultra sound or something else and then hope you would find it or an MR and try to figure out how to biopsy that. But I do think that this a little more aggressive than I would be in terms of the indication if costs are really limited because I think it might have to be refined further to define an extremely high risk group of women and even in that group I think it might be better to it as part of a study—that is just my opinion. I should add though that in some women, women with silicone implants, there aren’t a lot of patients with specific problems but I think that in that setting PET is probably a little better and there are a few more specific studies done. We have a paper in press coming out looking at the intensity of normal FDG uptake by age and it clearly declines in an age-related fashion. So certainly some young women have fairly high SUVs throughout their breasts as Dr Shreve pointed out and that is why I am a little bit reluctant on the very broad descriptive use in that group.

Floor: Simon can I make a comment, I would absolutely agree with that point, particularly if the sensitivity at best from reading the literature is about 85%, probably less for tumours that are T1 or so. You cannot avoid not doing a biopsy in these women with potentially curable disease should it be small enough. So I am not really sure enough how a PET scan if it is positive you are going to biopsy, if it is negative you are probably going to biopsy anyways, I am not really clear how PET scan in this specific scenario is going to help your clinical decision making, because the risks of not biopsying are too high in my own feeling.

Floor: If I might add something to that as well, the PET scan sensitivity for axillary node and it seems the avidity for breast cancer tissue is not very high. We have heard a lot of data presented today about FDG, has there been any work done at all with the other markers like the amino acids, you know are there other PET tools that are more sensitive for picking up metastatic disease or identifying smaller T1 lesions in dense breasts for instance?

Dr Wahl: Well I think those are research questions and I think they are highly relevant questions but right now the small lesions are a problem even with dedicated breast PET imagers which Paul talked about, phantom studies have shown that you still having difficulty in detecting lesions under one centimetre with the typical uptake levels seen with FDG. So I think that there is interest in looking at other agents which have a lower uptake in normal breast. The studies done with pyresene and methenamine and even thoresodial have been limited. They do show promise but they have been very small studies so I think they are too preliminary that you would want to try to adopt them routinely.

Floor: Simon if I could say something, its Karen here, I think the whole breast issue is obviously very complex as shown by the fact that it hasn’t been approved for funding south of the border in many ways and I think what we have come up with really is a bit of an individualized question. I think there is the question of we can’t just abandon this tumour site obviously there are a number of situations where it is of relevance, but it is really an individualized situation of diagnosing otherwise difficult to diagnose areas. I think what Steven said is very important in terms of needing to biopsy anyways, I think what Vanessa summarised otherwise is very individualized cases of metastatic diseases not otherwise diagnosed and I think that at the end of the day we have to be very practical, that this is a place where we want to have some impact on our management, we want to use PET sensibly in those cases where it may impact on our management. This is a huge group of patients and therefore I think that we have to be quite responsible in doing it that way.

Dr Conti: May I add also that next week we present our case to HCFA on breast cancer the 19^th June, and the, basically the discussions have been thus far to present two indications. One is in the dense breast surgically manipulated breast and the second one is in the issue of staging, excuse me, in re-staging and detection of recurrent disease. Those are the two areas that we want to discuss with Medical Advisory Board to HCFA, next week. My own feeling on the dense breast issue is again an individualized approach, that in cases that are diagnostically difficult if you will, and some of those cases may or may not be amenable to biopsy, for example the presence of an implant, those types of cases; so you might want to consider—of course breast cancer is going to be one of the ones you are going to go after surgically and you are going to go after these cancers with biopsy and don’t want to interfere with that standard of care to any great degree except where it is potentially well demonstrated that it can be avoided and not necessary.

Dr Sutcliffe: Thank you Peter. It would seem that maybe we have to take a fairly pragmatic approach to breast cancer in terms of indications and estimate a percentage complexity factor as being the determinant of utilization to answer to specifically directed questions.