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SLIDES
& TRANSCRIPTS
Wednesday
, June 20
PATHOLOGY/CORRELATIVE STUDIES PANEL SUMMARY
Edward Gabrielson,
MD
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| Slide
1: Objectives |
 DR.
SAXMAN: Okay, Dr. Gabrielson is going to summarize the pathology
and correlative studies section.
DR. GABRIELSON: I am sorry to say that I have four slides, and
it is all the fault of my panelists. There are so many recommendations.
For pathology we have generally two areas of objectives. One is
to improve our diagnosis and another is to understand the biology
of what is going on better. In the ideal world we would like to
be able to assess accurately what is going on in one of these
lesions with just a needle aspirate, with a small amount of material,
tell the treating physicians whether or not this lesion needs
a wide resection, a lobectomy, whether it needs adjuvant treatment
or whether it can be treated by a very limited resection. So,
being able to accurately assess these lesions is important. It
is also important to be able to correlate this with radiology
data so that with the radiology data we can really accurately
predict what would happen to these lesions if treated with limited
resection.
We, also,
in the ideal world really want to understand the biology of all
this better because ideally we would be able to give the chemotherapy,
chemoprevention people some ideas of new targets. We would also
like to help people develop some models, perhaps mouse models,
for development of new treatments in chemoprevention.
As far as
recommendations are concerned, this is where we have the three
slides. First of all we need to develop a standardized approach
to specimen collection and handling. People aspirate lesions in
different ways. We handle the resected specimens in different
ways. So, we do need to develop some standardized approaches here.
We, also,
need to develop standard diagnostic criteria and definitions for
small lesions especially these adenomatous lesions. We don't even
have a standardized definition for atypical adenomatous hyperplasia.
We need to develop molecular markers for the small adenomatous
lesions and some areas we could look at would include FISH, aneuploidy,
gene expression. It doesn't necessarily have to be with gene arrays.
It could, also, be with immunohistochemistry and in fact tissue
arrays could be very helpful here.
Another thing
that I think I heard Madeline throw out yesterday and then it
was just dropped, we would ideally be able to have some molecular
assessment of resection margins and that is something that we
should look at here.
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| Slide
2: Recommendations |
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 So,
for specific recommendations; one is to start with a multi-institutional
registry of the pathology and all this pathology should be correlated
with clinical history and outcomes, particularly long-term outcomes,
and have continuous updating of the radiology and imaging data.
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| Slide
3: Recommendations |
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 Echoing
what Paul brought up, if this is done outside of clinical trials
it is doubtful that we are going to get this information and that
pathology is going to become less and less meaningful.
We should also develop a high-resolution pathology image database
and actually that one slide that I showed was a composite figure.
We could easily image lesions that are 1 or 2 centimeters at high
resolution so that any pathologist anywhere in the world, if a pathologist
in Anchorage, Alaska is bored he could go look at all these lesions
at high magnification and maybe somebody even outside of a multi-institutional
panel would come up with some useful ideas for assessing these.
We could also share all of our data with our colleagues in Japan
who have a lot of experience in this area. We should, make pathology
tissues available for molecular studies and we should always have
some paraffin tissue available, hopefully in some cases some frozen
tissue available. We should also consider getting scrapings of margins
for some molecular studies. Ruth Katz brought up a very good point.
We should probably include all stage I lesions, not limited arbitrarily
to something less than 1 centimeter because I think we are looking
at the biology of small lesions in general.
DR. BUNN: Is
that IA? You have IB in there.
DR GABRIELSON: I will change that, Paul.
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| Slide
4: Recommendations |
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Moving forward with some more specific recommendations, one is to
develop some tissue arrays for the stage I lesions for evaluation
of molecular markers, and again, we need all of this correlated
with clinical outcomes. It would be helpful to have a panel for
review of the lesions and recommending standard diagnostic criteria.
This is not a new concept. It has been applied to many other areas
of pathology.
It does improve standardization and it does improve diagnosis, and
finally I think everybody is going to put this on their slides,
we need to develop a relational database that can correlate pathology,
radiology, outcomes and the molecular data, and that is really the
only way that we will be able to collate all of this and understand
what is going on.
DR. SAXMAN: Any comments, clarifications?
DR. STEVENS: Yes, one thing that it would be nice to have as well
is normal tissue on some of these patients and that that might be
a component of your tissue database as well so that we can ask some
basic questions about why these people get cancer.
DR. GABRIELSON: That is a very good point. We should, also, be considering
perhaps some genetic polymorphisms and predispositions to cancer.
So, that could be included in our collection of pathology.
PARTICIPANT: So, pathology for molecular studies with normal tissue
as well as cancer tissue.
PARTICIPANT: Just one comment about all stage I lesions other than
IA probably is less than 3 centimeters or better because you have
IB which is pleural invasion involvement less than 3 centimeters
and this is IB. T2 includes a lesion which is less than 3 centimeters
but with pleural invasion.
DR. STAAB: I would just like to make a comment about the lung imaging
database consortium. This is a mechanism that was funded by NCI.
It is primarily related to the imaging components but there is related
data involved in it. The consortium steering committee had its first
meeting last week. There are five institutions, I believe involved
in developing this database. It is primarily developing a database
of small lesions and we will go forward from there.
DR. SAXMAN: Any other comments?
DR. COLE: In
terms of the pathology role, just two comments. In addition to the
molecular profiling of the primary tumor in terms of risk assessment
the pathologist will also play a role in looking at occult systemic
events which I think will be very useful not only in assessing risk
of progression in these small lesions but also could be a useful
tool as an intermediate marker of therapeutic efficacy. So addressing
some of the issues with regard to how will we assess therapeutic
efficacy in the short term. This is being used in some tumors and
I think could be very useful in these areas.
The other issue with molecular profiling I think that needs to be
considered has to do with the mechanism-based therapy and that is
to make sure that we include not only risk assessment but also assessment
of therapeutic efficacy in terms of the mechanisms of some of these
specifically targeted therapies so that as we begin to design the
trials for these small lesions we can design them on the basis of
not only selecting patients on the basis of risk but also on the
basis of potential response to the various therapies that might
be offered.
DR. SAXMAN: Any other comments?
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