 DR.
SAXMAN: Thank you. We need to move on. Deja vu all over again,
I guess from this morning, but I am sure that based upon the discussion
this morning Paul has some other thoughts. So, we will let Paul
summarize the chemotherapy discussion section.
DR. BUNN:
One of the things I think that struck all of our attention is
the studies that were presented all had a handful of patients.
So, you know, there aren't zillions of these patients actually
and these patients are valuable resources that cannot be wasted.
I think in terms of coordination the patients that are going to
go on trials like we just heard I am not sure the mechanisms that
were set up to look at screening are the appropriate mechanisms.
Maybe they are, but we need to figure it out because really the
question is we are not going to create a new mechanism and the
question is when the patients are identified are they going to
be followed by those registries or then are they going to go to
ECOG and SWOG and RTOG or what is the central mechanism for collecting
these patients and following these patients?
So, to me a big thing is to figure out once patients are identified
who is going to follow them, and this is not 6 months of follow-up.
We are talking 10 years of follow-up. So, there has to be some
statistical center that has the expertise and the experience with
following patients coming from all across the country. It seems
to me we need to figure out once patients are identified, these
are patients who have got these small nodules, they cannot be
lost. They have to be followed by somebody, and we have to figure
out who it is that is going to follow them.
Is it some Intergroup mechanism? Are they all going to be followed
by ECOG? Are they all going to be followed by ACOSOG? Are they
all going to be followed by SWOG? Who cares, but there needs to
be a coordinated way of identifying these patients and following
them clinically forever. Otherwise they are going to be completely
wasted. Patients are valuable resources that cannot be wasted,
and all of them should be entered on a clinical trial which may
only be a follow-up cohort clinical trial but all of these patients
once they are identified should go on to some kind of a follow-up
study.
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 Now,
my interpretation of the consensus was that indeterminate nodules,
people that have small nodules that cannot be biopsied and we don't
know what they are, whether they are solid or partly solid should
go on to some kind of a cohort study which is a cohort registry
follow-up study. My conclusion is that those tumors that are biopsied
and are of uncertain invasiveness should also go on to some kind
of a cohort registry trial and should be followed without any definitive
extra studies.
This may not be a uniform or a unanimous consensus, but I believe
those that do have invasive cancer should be eligible for therapy
trials and should be entered on therapy trials. I think those that
are medically inoperable should have the type of study that has
just been discussed. I, personally wouldn't have any problem putting
a patient like that on stereotactic radiosurgery trial. I think
it would be completely appropriate.
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Those patients
are going to be followed anyway. They need to be followed, and I
personally believe that you could follow these biomarkers in a randomized
way so that half the patients were getting COX-2 or EGFR inhibitor
and half weren't and you could see what happened. You could correlate
the biologic markers with both recurrence and second primaries.
So, I, also, think that some pilot trials in these patients of the
type that Dr. Mulshine was talking about would be reasonable as
well, but again no single institution and probably no single cooperative
group as it currently exists would have enough patients for any
of these trials. So, we need some kind of mechanism that once these
patients are identified that they are going somewhere to be followed
and going somewhere where they can go on a clinical trial and again
I don't know whether that ACOSOG, ECOG or who that is but I think
for the NCI that is really a point of discussion. It could be one
of the registries but there needs to be some way where these patients
are followed and eligible for trials.
DR. SAXMAN: Any other comments?
PARTICIPANT:
I just wanted to mention that I thought Dr. Reeves' data and the
ability to measure 3 to 5% change in a lesion is ground breaking
in terms of our ability to do 6-week trials or 2-month trials or
whatever the ethics or standard of care would allow in whatever
setting it allows it. You have the ones that are biopsied and proven
cancer. Certainly you have disrupted the lesion, but you still probably
have an opportunity to see what happens to that lesion over 6 to
8 weeks and everything that we know about pre-cancer, cancer is
the best parameter for integrating what is happening is change in
lesion size that measures the dynamics of cell division and cell
death. It is probably going to predict better than anything else
we can measure and certainly whatever else we measure in terms of
the biomarkers could be correlated with that phenomenon.
So, I just think when people can measure 3 to 5% change in volume
that that kind of research needs to really be fostered and encouraged.
DR. BUNN: I agree and then you take the nodule out so the pathologist
can correlate what actually happened with whatever intervention
you did with the changing size in the nodule when you have the nodule
in the pathologist's hands.
PARTICIPANT: I would like to second that. I agree absolutely with
what Gary has said and Dr. Korn I think has left but we have been
chatting with him with Claudia and David about coming up with some
new trial structures to take advantage of that brief exposure with
the drug evaluating response in that setting. I would also point
out that Larry Summers and some of the people working with Dave
Schrump have been looking at virtual bronchoscopy and I think that
is going to give you another target to look at in terms of looking
at endobronchial response and we have got to develop new trial mechanisms
around that to address this area.
DR. BUNN: But again the question was raised in the radiotherapy
section are there enough patients and that is a major issue. Certainly
I can tell you the University of Colorado doesn't have enough patients
to do a trial, but certainly if there was a mechanism for every
patient like this that we identify or gets referred to us we would
love to put them into the registry for the indeterminate nodules
and the non-invasive cancers and a treatment algorithm. Nasser indicated
that at Cornell, and I don't know if somebody from Cornell can correct
him, but he was saying at Cornell you are probably talking 10 of
these patients a year. That is probably true for all our institutions.
So, this is going to have to be coordinated nationally by the NCI
through one mechanism or another.
David Harrington, can ECOG do this? Would ECOG be willing to do
this?
DR. HARRINGTON: It turns out that with these sorts of patients the
follow-up is less difficult for us than the registration especially
when patients like this are seen by many different modalities. ECOG
is primarily a medical oncology group. So, it is the entry point
that is the tough point, capturing patients who are seen by many
different specialties.
The follow-up mechanisms exist in any of the groups, I think. It
is a well-oiled machine, but it is getting them in there first that
is the hard part.
DR. BUNN: Yes, and the question is how do we coordinate this? Do
they go from one registry in there into one registry and follow
them forever in clinical trials? How to get it incorporated into
those registries? I don't know. I think that is something the NCI
needs to be discussing.
PARTICIPANT: Also, I would agree with the small number. We only
had three out of our first year of 1500 patients and also from our
standpoint our expertise in fine needle biopsy is not at the clinic.
So, we don't have David unless he wants to come to Rochester in
January to do that for us. So, our problem is that biopsy is more
than likely going to be done fluoroscopically. So, the pre-op treatment
would be thrown out for us, and we would be in that postoperative
for the COX inhibitor. But it is going to be a small number. So,
I think it is the Intergroup or the American College of Surgeons
that is going to be the key.
PARTICIPANT: First of all I wouldn't let David go up there in January
but I really think that is why in an institution doing screening,
they should be collaborating and that is really the place that you
can identify them. Then if we can develop a follow-up to the other
organizations that would be very good, but it is relatively easy
to do at the screening setting and particularly with the growth
that you can then assess in a central fashion.
PARTICIPANT: One thing we didn't really touch upon is just how difficult
it is to get tissue from these patients for the pre- and post-assessment
process. If we are talking about lesions of less than a centimeter
even if you spin it down or have a cell block you are not going
to be able to do hundreds of biomarker studies. So, probably if
we are going to do trials where we want to follow biomarkers we
want to do them in larger lesions like for example head and neck
tumors larger than 3 centimeters, 6 centimeter tumors before we
get to this stage.
We want to have a pretty clear plan of exactly what we want to look
at given the paucity of tissue we are going to get from the pre-biopsy.
DR. SAXMAN: Thank you. I would just make one comment, Paul. I think
you are absolutely right that the NCI needs to assist in coordinating
these efforts but I hear that ASCO has a president who has an intense
interest in lung cancer and I think that one possibility is that
ASCO could take some type of leadership role in some part of these
efforts as well. That they be something worth considering at some
future date.
PARTICIPANT: Scott, I think that is exactly correct. I think that
as long as our next president of ASCO is here the other issue is
that I understand he has reasonable credibility with the pharmaceutical
industry and they are really not participating in this opportunity
because of the problems with liability and the trial design and
the FDA validation. We need to have some further dialogue around
those points to try to decompress those issues.
I think one incredibly important document that the Institute of
Medicine just published is about health care delivery in the United
States and a lot of the problems that they identified as being really
particularly severe are choke points for the development of this
kind of prevention research. I think the big thing that they point
out is that infrastructure isn't in place to coordinate these things
and the second thing is there are disincentives for pharmaceutical
participation in some of these areas. I think that has got to be
addressed.
DR. SAXMAN: Okay, thank you. I wanted to spend the last few minutes,
we are out of time, discussing some people's feelings about how
this forum worked and how valuable this was.
I think because we are out of time and I promised to end at noon
that we will use the evaluation forms for that.
So, please, if you would take care to make comments about the value
of this forum for you and the issues that came out of this and comment
as to how you think this might be better. Before you leave if you
would please join me again in thanking all of the people that put
this together, not only the NCI staff but all of the planning teams
and all of the speakers and everyone. I think they all did a terrific
job.
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My
own view is those that have definitive therapy or are going to have
definitive therapy and have definitive invasive cancer should be
eligible for trials. I think that a trial could be done and should
be done looking at either a COX-2 inhibitor or an EGF inhibitor.
