Summary




SLIDES & TRANSCRIPTS
Monday, June 17

Keynote Speaker


Andrew von Eschenbach, MD
Slide 1:

DR. SAXMAN: We are very privileged to have Dr. von Eschenbach here to address us this evening to discuss activities of the NCI, both related to sarcoma as well as overall directions for the Institute. It is an honor for me to present the director of the National Cancer Institute, Dr. Andrew von Eschenbach.

[Applause.]

DR. VON ESCHENBACH: Yes, it has been a bit more than 100 days, still standing, and truly still absolutely exhilarated by the opportunity to be here.

This has been an incredible experience for me because, having spent the last 26 years of my career at M.D. Anderson, I was completely new to the NCI. Yet, what I found, in coming to this incredible organization, is that its culture was very much like what I had been used to. It is made up of absolutely extraordinarily talented people who have a very definite sense of mission and of commitment to service, and that is exactly what I came from. It has felt very much like being at home. I have really tremendously enjoyed the opportunity to begin to contribute to the NCI and to its agenda.

What I wanted to share with you tonight is, first of all, I am really very pleased to be here. What you are about is extremely important to our overall agenda, and to have a few moments to share with you some of the perspective that I have is for me a great opportunity. So, I thank you for the invitation.

What I wanted to do tonight was to basically share a message with you -- that is, a message that I have been trying to communicate in a variety of places and to a variety of audiences. Because I really think that it is at the core of everything that we are about, that will truly be changing the face of oncology for the future.

I use the words "strategic inflection" as a way of framing this discussion. I really truly believe that we are at a fundamentally different place in oncology than any of us have been used to in our careers up to this point in time. The concept of a strategic inflection in biology has profound implications for all of oncology and particularly for soft tissue sarcomas.

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Slide 2:

The way I think we need to embrace this concept of a strategic inflection is to realize that we, as a society, are extremely privileged at this point. That privilege carries with it a very profound and very important purpose, in that it is based on the fact that we have had significant progress up to this point in time that has led us to unbelievable possibilities for the future. The only way in which we'll realize the full fruition of this strategic inflection is by creating partnerships and collaborations and relationships that bring this all together.

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Slide 3:

With regard to privilege, one of the exciting things for me is to come to the National Cancer Institute at a time when it is appropriate for us to step back and realize that we -- as a country, as a nation, that have made this investment in an entity like the National Cancer Institute -- we, as a nation, are unbelievably privileged.
We truly are blessed by having an abundance of resources, financial as well as, more important, incredible resources with regard to our talents and our gifts. We have the opportunity now, with organizations like the NCI, with leadership that is reflected in the people who are sitting in this room -- you -- we now have unbelievable privilege.

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Slide 4:

It is privilege that has a purpose. This is not a gift that has been given to us for idle purposes, but for purposes that truly reflect on one of the most fundamental problems that faces us as a society. You and I are keenly aware of the suffering and death that is occurring around us because of this disease called cancer, and we have the privilege and the purpose to now, in this time and in this place, be able to fundamentally change the face of this disease.

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Slide 5:

The reason why we can do that is because of the opportunities and the progress that has been made thus far. You and I know the statistics and we know the numbers. We know what an incredibly significant problem this is. We also know that behind each of those statistics is a face, a living human being that you and I have been entrusted to look after,

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Slide 6:

and in particular -- with regard to the disease that you have focused on for purposes of this meeting -- although the numbers are smaller in magnitude, that does not diminish the pain and the suffering that those individual patients are experiencing . Our commitment is to those human beings who are destined to suffer and die of this disease, unless we seize the opportunity.

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Slide 7:

It is even more important for us as Americans. Given the gifts and talents that we have in this country, it is the recognition that, for us, we have a responsibility to the rest of the world. There is a global burden of cancer that we, in this country, have a responsibility to address. So, what we are about is not only the statistics as they apply to the United States, but the statistics as they apply worldwide.

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Slide 8:

We can begin to think about truly addressing this problem because of the fact that we have made significant progress. What has occurred, and what has led to this strategic inflection is that the investment that we have made up to this point in time in biomedical research has truly fundamentally changed the course of cancer and hopefully expectedly may even change the course of civilization.
Let me tell you why I think it is important to seize this opportunity and what this is about.

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Slide 9:

I borrow from an example that Andy Grove uses, called a "strategic inflection". He wrote about this in his book on management that is called Only the Paranoid Survive. He talks about the fact that, in the course of a business or industry or even a civilization, there are moments where there is what he describes as a 10X change in the field.

He talks about winds of change that are constantly occurring that influence the trajectory or the course of a business or a society. There are particular moments that occur when that wind of change is really and truly a typhoon. That creates what he describes as a strategic inflection, which, if it is grasped and understood and appropriately responded to, will put that business or that civilization on an exponential trajectory of growth. If it is unrecognized or unappreciated, that business will go into a decline, or that civilization will miss a great opportunity.

In the computing industry, he described a strategic inflection as the introduction of the microprocessor. What my thesis is, and has been, and the message I have been trying to communicate, is that we are at a strategic inflection in biology based on this investment in biomedical research. If we understand the implications of that inflection and grasp it, we have the opportunity to really embark upon an exponential advance.

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Slide 10:

To put it in a little bit of historical perspective, let me draw a couple parallels. If you go back to the turn of the 20th century, what you see historically is science's fundamental quest at that time was to understand the nature of matter. Physics was the queen of sciences, with the atom and the nucleus being the focus of study. We all recognize historically what occurred in the early part of the 20th century, when the mysteries of the atom were revealed and the nucleus was opened, if you will. That created a strategic inflection which fundamentally has changed the course of civilization from that point forward.

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Slide 11:

If you fast forward 100 years to the turn of the 21st century -- this century -- we begin to see an interesting parallel. Instead of the quest of science being the understanding of the nature of matter, the quest is to understand the fundamental nature of life. We have switched from a focus on physics to a focus on biology and molecular biology and genetics. Instead of the atom, we have focused on the cell, and we are, in fact, just as they did, beginning to reveal the mysteries contained within that nucleus, and the human genome project is a classic example or understanding of that impact.

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Slide 12:

So, we have recreated another strategic inflection, only this time in biology, and we have created -- or are in the process of creating -- this unbelievable change that can fundamentally alter the course of disease states like cancer, as well as others, and fundamentally will change society. One doesn't have to pick up the newspaper to read about cloning and stem cell research, et cetera, to start to realize the implications of all this.

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Slide 13:

The fact is, for our purposes, today we are poised today to fundamentally change our approach to oncology because for the first time we are beginning to understand cancer at its fundamental, genetic, molecular, and cellular level. This is opening up a true revolution in our ability to deal with the disease.

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Slide 14:

One of the implications of the strategic inflection is that it has changed our approach to cancer from the paradigm that I grew up in, when I started at M.D. Anderson in the mid-1970s, which was the paradigm of "seek and destroy". Our approach to cancer in this past century has been find it and kill it, and find it as early as you can and kill it as dead as you can. We have essentially been trying to refine and integrate our weapons of destruction in order to get the best possible outcome, and no field has probably been more aware of that struggle than the field of soft tissue sarcomas.

In spite of tremendous progress that we have made in our ability to manage these diseases with some successes, we recognize that we haven't fundamentally conquered the problem. That certainly is true in my field, in prostate cancer, when radical prostatectomy was introduced into this country in 1904. We are still dealing with prostate cancer fundamentally the same way 100 years later. We haven't solved the problem.

What this strategic inflection and this revolution has produced is a paradigm shift from "seek and destroy" to now what you, at this conference are working to further unfold, and that is the paradigm of "target and control".

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Slide 15:

We fundamentally are approaching cancer by virtue of the fact that we now understand the fundamental steps and processes that give rise to a malignant transformation, and each of those steps and processes open up for us a target for which we can create an intervention that can either prevent, impede, reverse, or halt the process.

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Slide 16:

We can begin to think now of our opportunity to control cancer much, perhaps, in the same way one could think about being able to interfere with a pentathlon or decathlon event, in which we have multiple places in this malignant process where we can intervene. We may very well see a paradigm that might not only intervenes at one, but at multiple places along the way, so that the net effect is to prevent the malignant cascade to a lethal phenotype of disease.

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Slide 17:

We have now opportunities at a variety of points, along this process, to deal with the proliferative events that occur within the cancer cell itself, its interaction with its microenvironment to create the process of invasion and tumor growth by, for example inhibiting angiogenesis and, more important, the whole phenomenon of metastasis based on specific epithelial stromal interactions, which open up a host of opportunity for us for interventions.

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Slide 18:


What we will see, hopefully, that we have not seen in the past 25 years of the old paradigm, is the continuing improvement in overall survival so that going into the next century these routes will not be flattened, but will actually accelerate and decline.

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Slide 19:

We have the ability, the possibility, to achieve this because of the progress we have made in understanding this fundamental basis of disease. That will open up opportunities not only for treatment but in detection, diagnosis, and prevention of cancer,

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Slide 20:

and it is all based on the tremendous progress that we have made in this investment in biomedical research.

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Slide 21:

There are implications, and these implications in particular, I think apply to the diseases that you are interested in. In the old model, we were looking for opportunities to eradicate or destroy cancers, and we focused on cancer-type-specific drugs with thinking of specific drugs for specific tumors. Pharma paid little attention in this kind of a model because of its economic implications, on developing attention to rare tumors.

In the new model, in this new molecular or biologic paradigm, we have the opportunity to completely reform the taxonomy of tumors. So, what you will see ultimately is not a taxonomy based on organ site, but a taxonomy based on molecular profile.

That opens up opportunities where interventions -- as you are already seeing in GIST -- the opportunity to apply an intervention to subsets of a variety of solid tumors. That creates a new portfolio with targets as our endpoints and pharmaceutical companies beginning to develop market share based on pathways cutting across diseases.

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Slide 22:

We have seen multiple examples of the ability to start this kind of drug development based on our understanding of targets that have been defined by virtue of underlying biology and, in your particular situation, the important implications of Gleevec as it relates to c-kit pathways.

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Slide 23:

So, Gleevec became for us, if you will, the proof of principle. The principle that, if you could understand the pathways -- the molecular pathways that were giving rise to an oncologic process -- we could develop a targeted intervention that could intervene in that pathway and produce the outcome that we desired, namely in terms of the ability to control the disease.

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Slide 24:

In your particular area, one of the very important parts of this component was the ability to work together collaboratively and cooperatively to test this new paradigm such that progress was made in what was essentially record time, and being able to apply the new model to what was, in your case a very rare tumor, one for which there really was no significant opportunity prior to this.

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Slide 25:

The other important implication, I think, that comes from this lesson that you appreciate the most, and it is a message that I am trying to communicate even more broadly -- especially with regard to those organizations like Congress and the pharmaceutical industry -- is to begin to appreciate that this new paradigm opens up for us not just opportunities with regard to therapeutic interventions, but presents incredible opportunities for us with regard to diagnostics, predictions of disease behavior, monitoring of disease outcome with regard to intermediate endpoints, and all of this technology really becomes an extremely important part of our armamentarium.

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Slide 26:

Knowledge of these pathways is also opening up the opportunity for the design of new types of agents that can intervene within the pathway. What we are beginning to see is, I believe, that we will have multiple agents working in an integrated fashion to attack pathways that are parallel or complementary.

So, in this particular case, those agents like rapamycin analog CCI-779 that interfere with the mTOR kinase pathway can be complementary to what is already available with regard to intervention in c-kit

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Slide 27:

We know that there is a variety of targets that will be identified in these tumors. As I pointed out earlier, we will see these targets applied across a variety of diseases. So, we will be reformulating our taxonomy with regard to selection of therapy. That will have profound implications on our ability to create the impetus for pharmaceutical contribution to development.

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Slide 28:

This is just simply to reaffirm the hypothesis that our current methods in the old paradigm of trying to chip away at the tip of the iceberg really have not fundamentally solved the problem. But if we are willing to think ahead to our ability to work below the surface, by elucidating the various pathways that exist that give rise to this tumor, and then attacking these individually and collectively, we will fundamentally be able to totally completely revise our ability to manage this disease.

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Slide 29:

So, that is the basis for NCI's emerging agenda. What we want to do is to maintain this momentum and accentuate it. We need to continue to invest and promote and exploit these new mechanistic discoveries. So, we will continue to emphasize our discovery-based investments, particularly with regard to investigator-initiated research projects or the R01 mechanism.

In addition to developing these individual, mechanistic investigations, we very importantly need to create the platforms for the translation of this information into these biologic-based interventions, be they for detection, treatment, or prevention. That requires the promotion of centers and SPOREs and consortia that create the platforms for the translational component, and also to actively, aggressively participate in the promotion of clinical trials, so that we see the delivery piece complementing the discovery piece.

I think there are associated challenges for us that have to do with our ability to make sure that we are going to have adequate work force in this new paradigm. So, training programs are going to be an important part of this agenda, and the opportunity and the realization that there are allied of disciplines that are going to be critically important to the full expression of the new paradigm. So, for example, we make substantial investments in promoting these parallel disciplines like bioinformatics.

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Slide 30:

The other important message that I want to leave with you with regard to NCI's agenda for the future is to not only focus on the individual parts of this problem, which we will do by focusing research that looks at the cancer cell and its biology, but also importantly recognizes that that cancer cell is functionally interacting with its host. The person is as important in this occasion as is the tumor. We have a tremendous need to further invest in our understanding of host factors, and the host milieu will be an important area of future emphasis and agenda setting.

There is also the interaction of the cancer, the tumor, the person, and the environment; and population studies are also an extremely important part of the portfolio. In addition to our investigation of these various components, it is extremely important that we begin to take a systems biology approach and begin to invest in our understanding of the interactions. There are systems biology approaches that need to be taken within the cancer cell itself, so that we understand the interaction of these multiple pathways; but there are systems biology approaches that need to be taken in the overall process.

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Slide 31:

The other component, in addition to systems biology that we will be emphasizing, is this concept that I am describing as seamless oncology. More importantly than ever in this new paradigm is the ability for us to seamlessly integrate clinical observations and laboratory investigations.

It is no longer a bench-to-bedside linear process. This will be a process that is much more circular, in which observations from patients must go into the laboratory for investigation, investigations in the laboratory translated back to interventions in the patients, and then the observation of the impact of that intervention at the bedside must go back to the laboratory for further investigation.
So, we will see this continuous process of observations of clinical significance, of mechanistic investigation, of biologic-based intervention and opportunity to apply that in the clinic, where we will be monitoring biologic endpoints and outcomes through things like functional imaging and molecular pathology. Then that information will go right back to re-inform the next set of investigations.

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Slide 32:

We need to also emphasize and promote the whole opportunity for drug development based on this new paradigm. We are working collaboratively and cooperatively with a group of individuals and efforts to be able to accelerate the process of speeding the discovery or the development of drugs based on this new biologic paradigm. There are multiple problems within this pipeline that need to be addressed, not the least of which is regulatory approval problems; but all of this is being looked at individually, and particularly with regard to target validation and our ability to develop appropriate models.

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Slide 33:

We have to have mechanisms in place, and we are using the Progress Review Group mechanism, and we expect and we anticipate a particular Progress Review Group to focus on soft tissue sarcomas, so that we can go through a process of defining what the appropriate recommendations are, creating an implementation plan for those recommendations, and then be able to determine outcome or output of those implementation programs, to be sure that we are truly impacting on this disease. This PRG process has worked well thus far in other tumor sites, and I am looking forward to it being a way of really defining the strategic agenda for soft tissue sarcomas.

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Slide 34:

I think we have to continue to evolve our thinking with regard to what must be accomplished in order to accelerate progress in these particularly rare types of tumors. One of the things that I think is extremely important is our ability to be able to molecularly image the pharmacodynamics of our interventions, and that is going to also be an area of high priority for us. We recently have made a significant investment in a new institute at the NIH, the Institute for Biomedical Imaging and Bioengineering, that we will expect to be working closely with, as we develop the imaging part of it.

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Slide 35:

Partnerships are obviously key to the success of the story, and we recognize at NCI that, in spite of the significance of our investment, we could not possibly do it all. What we want to do is to make sure that we partner to see to it that all of it gets done.

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Slide 36:

The discovery piece is where we will make our primary contribution and investment and that we believe is our essential responsibility. It is also critically important that we play an important role in the dissemination and development of interventions, based on this discovery, and to be certain that those interventions are being delivered appropriately to populations of need.

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Slide 37:

So, we will play a role across this entire dimension in an effort to make it seamless and to be able to be assured that we are continuously exploiting the new paradigm and making certain that we get done what needs to get done.

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Slide 38:

It is a time of great privilege; but it is a privilege that has an important purpose associated with it. It is realistic to expect that we truly can make a difference, because we simply have to look at the progress that has occurred and extrapolate it, to begin to appreciate some of the possibilities that are before us. That strategic inflection curve is, for me, an achievable reality if we can come together, work collaboratively, and fully exploit the implications of this revolution in biomedical research.
We will make the investment to work collaboratively and cooperatively with you, to make sure that all of that gets done with regard to specifically, the issue of rare tumors like soft tissue sarcomas.

I appreciate the opportunity to come and give you that perspective so that you have a little sense of the rationale and reasoning as to what it is that I think we will be focusing on and paying attention to, in these unfolding next few years, and I very much look forward to your continued collective and individual input as we shape this agenda in what I truly believe will be an important collaboration and partnership. So, thank you for the time and the opportunity to be with you.

[Applause.]

DR. SAXMAN: Does anyone have any questions for Dr. von Eschenbach?

PARTICIPANT: I think you have encapsulated something that we all feel by our presence here today, and I very much appreciate your thoughts.

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Slide 39:

DR. VON ESCHENBACH: I knew what you were in the process of discussing. It almost seemed like I was bringing coals to Newcastle, because this is a concept that you are living. I thought it was important to share, in a strategic kind of way, to make you realize, or drive home the message, that what you are doing you are not doing in a vacuum, in isolation. What you are doing is fundamentally at the core of what I believe we, as an institute, need to be doing, and will be doing as we go forward, and why it is so important that we do it.
Your role -- I think, sometimes, dealing with soft tissue sarcomas and not prostate cancer, we wonder whether anybody is even noticing. Well, you in fact are pioneering the new paradigm. When it is said and done, you are going to be at the core of it rather than the periphery of it.

DR. SAXMAN: I think one of the critical things to this group, because of the rarity of this disease, is the issue of international collaborations or, as Dr. van Oosterom likes to talk about, across the pond. Would you care to share your thoughts about that?

DR. VON ESCHENBACH: The international collaboration is an extremely important issue for a couple of reasons.

One, first and foremost: it is an important agenda for the administration. Prior to President Bush being elected, as the campaign was being formulated, there was a very interesting panel discussion about what the future challenges were going to be for our foreign policy.

Lawrence Eagleburger at the time said that he thought, having just read an issue of Scientific American, that this incredible revolution that was occurring in technology was positioning this country so far out in front with regard to what we had available to us, that if we didn't figure out a way to be able to share that with the rest of the world, that the gulf between us and them, the haves and the have nots, was going to widen so much that we would only further accentuate the hate and resentment and envy, if you will. So, the term that was brought up at that point was how can this country export its excellence without arrogance?

The President picked up on that. I think it was only further heightened by 9/11. What his expectation is, is that we as a country will export this kind of excellence, but do it without arrogance.

It is also appreciated that we have something to offer but we have also a great deal to get back and receive. I think the point of it is that we can see that this is an international effort. Cancer is a global problem. We have something that we can contribute; but by partnering internationally, we will be able to accomplish so much more together. So I think it is the administration's philosophy that we should be pursuing this. It is kind of like my marching orders from on high; but it also is obviously so important because it makes so much sense to do it that way anyway. So, we will be paying a great deal of attention to our international effort.

DR. CHRISTOPHER FLETCHER: All of us are very excited about all the basic science discoveries that we all read about. None of us question that. But there is an enormous gulf between what we like to read each week in the journals and what most patients in the United States or elsewhere have access to. That is not just a fiscal phenomenon. It is the fact that huge numbers of discoveries, which we all like to quote at meetings like this, never get validated in the broader patient population. Nobody says, okay, we have discovered that, and let's go test it in 50,000 of these people, which is actually what translational medicine really is at the end of the day. It really is the bench-to-bedside stuff. We are prone to giving lip service to that without actually supporting it. Do you see that as one of your new priorities?

DR. VON ESCHENBACH: Yes. It is maybe not a new priority; but it is a high priority for me. We are trying to address it in a couple of different ways. I alluded to the fact that, in this concept of discovery-to-delivery, that in my view there is a need for certain platforms that can network and be able to disseminate and test these various interventions.

So, one of the things I have been working at is that there is a effort underway that is being primarily driven by a collaboration between the CDC, the National Cancer Institute, and the American Cancer Society, to create State cancer plans. That is being driven through the National Governors Association. Tom Ridge, before he took over homeland security, when he was governor of Pennsylvania, and Governor Barnes in Atlanta, have been the two governors to drive that.

They are creating State cancer plans that will incorporate this dissemination piece. What we need to do is wed and integrate into that process the translational platforms at cancer centers, so that you have the network to be able to do that dissemination and create those registries and abilities to deliver the drugs in the community, but also do it in a clinical trial setting.

The second thing is, we changed our clinical trials process so that any physician does not have to be a member of a Cooperative Group and can enter a patient onto a clinical trial. So, we are trying to broaden the network that way.

Then the third piece is to work collaboratively with the cooperative trials groups, to be able to increase and overcome some of the barriers that may exist to access to clinical trials. We are in the process of launching another collaborative effort in which the National Cancer Institute -- we just had to come up with an interesting way to be able to do this, because there wasn't a mechanism in place to be able to do it because of federal regulations. What will occur shortly, having signed off on the Memorandum of Understanding is, five pharmaceutical companies are putting up a total of $3 million. The NCI will put up $3 million to create a $6 million pool that will be able to award supplements to cancer centers for the specific purpose of looking at barriers to accession to clinical trials in this paradigm, and what works most effectively to get rid of those barriers. So we are attacking this in multiple places, in an effort to be able to get to exactly to where you want to be, which is that continuum from discovery to delivery.

DR. CHRISTOPHER FLETCHER: I think the other thing is, too, there is no doubt there is a better and better clinical trails infrastructure, but what has never been to date -- really tested -- is whether we can have an infrastructure for new diagnostic and prognostic approaches. Sarcoma is a good example. As you now know, we now like to diagnose things by genetic aberrations that can only be identified in a small number of laboratories. And so right now there is no means to look at large patient numbers. One almost needs clinical trials of diagnostic and prognostic approaches, not just therapeutics. It is almost a whole new thing.

DR. VON ESCHENBACH: The diagnostic piece that we are working on is not quite on the point that you are making, but it is close to it. We have recently partnered up with the FDA and introduced a couple of novel mechanisms whereby NCI will actually serve as a reference laboratory for the dissemination and development of the clinical trials of the diagnostic tests that Lance Leota has developed looking at protein profiling. So, we will be able to tremendously accelerate a broad-based clinical application of that technology beyond ovarian tumors to a variety of other tumor sites. The way it will be rapidly accelerated is by this mechanism, where FDA and NCI will partner and collaborate, so that we can administer the trial and be the reference laboratory all at the same time. That is going to triple the speed at which we will be able to carry those trials out, and get them out into the public.

You are absolutely right on the mark. One of our challenges is to keep finding creative ways to get outside the box. If we stay in the old box, we can't get there. We have to figure out new ways to do business, and that is the challenge.

ROBERT BENJAMIN: Andy, Sarcomas have always been a stepchild of U.S. Cooperative Groups, since they are a stepchild of oncology, representing a very small fraction of all patients. There is a French sarcoma group, there is a Canadian sarcoma group, there is an Italian sarcoma group, there is a Scandinavian sarcoma group, and the EORTC has a large bone and soft tissue group. None of the U.S. Cooperative Groups have a big effort in the treatment of sarcomas. We all meet together in an organization called the Connective Tissue Oncology Society. We all talk to each other. We are all anxious to cooperate with each other and do some specific studies together, but there is no mechanism. Has the NCI considered having a sarcoma study group for the United States, which is the only country that doesn't have one?

DR. VON ESCHENBACH: To be honest with you, I can't answer that question. I don't know. I think the point of the PRG process is to surface exactly those kinds of initiatives. If there is sufficient buy in, I don't see any reason why that couldn't be an option. But I don't have any specific knowledge of where we are in our thinking along those lines. I would have to ask. That hasn't come up in my first 100 days.

ROBERT BENJAMIN: It is surprising that sarcomas came up in your first 100 days.

DR. BORDEN: We are a little more than halfway through our deliberations. My sense is that we are going to come out with some pretty good recommendations for you.

We don't all have a really good sense for how State of the Science meetings recommendations move forward. Do we have to wait until 2003 for the Progress Review Group to act on the recommendations that may come out of this meeting?

DR. VON ESCHENBACH: Not having any history, personally, I am not giving you a historical answer to the question. I am giving you my personal answer to the question. No, you will not have to wait for that to occur. As this group deliberates and comes forward with recommendations and suggestions, I will make sure that they get immediately processed into the agenda, so to speak. I am a surgeon. It is not my style to do another test or get another opinion. Give me a sense of certainty and we will operate, we will do it. I am much more action-oriented and I just think that is appropriate. I don't expect you to sit and do all this and file another report. My pledge to you is to act on things as they are appropriate.

DR. DEMETRI: Dr. von Eschenbach, what this community has done with GIST has really shown, I think, the significance of this rare disease as a paradigm for some of the new approaches, and the translational approaches that can come out of these unusual tumors. What I would ask you is that whether, with this sort of power, you now feel that you can go to Congress and get new allocations of resources for this work, or whether you feel this is going to be a reallocation of current resources?
I think what you are seeing, with the data that you have alluded to, is really fairly breakthrough stuff that may have applicability to other more common tumors; but this is a rare disease. I would like your thoughts on it.

DR. VON ESCHENBACH: That is a very complicated question, to take it head on. First of all, what we are in the midst of now is, in 2003, if Congress approves the President's budget, NCI's funding goes from $4.2 billion to $4.7 billion. The problem is what is being anticipated for 2004, which is -- now that the NCI doubling has been achieved -- the expectation is that there will be a leveling off and the leveling off number for subsequent increases is 2.2 percent. In fact, when one looks at what that means, it is not a leveling off. It is actually a decline. You know how the process works, so I won't get into it.

So, we do have a disconnect. The disconnect is this story I just told and this strategic inflection requires us to not decline, but it requires us to seize this opportunity and to really continue to drive the progress. What is missing in the equation is, it is necessary to tell the story. I think that most people on Capitol Hill are understanding this. They have heard about Gleevec, et cetera, et cetera.

What they are asking us, what they asked me constantly during the appropriations is, can you show me how this investment that we made, how all this discovery that you are telling me about, translates? Not say just give us more money, but to be able to draw that trajectory and demonstrate what that money can, in fact, and will, in fact, accomplish and deliver on it.

So, no, we are not there. We are in jeopardy because there is the sense that, well, we gave them what they asked for. They wanted a doubling and we gave them the doubling. What is the problem? We have to reframe that, but we are going to have to reframe it with an administration that is very much more businesslike-oriented, and wants to understand return on investment and accountability.

DR. SAXMAN: Please join me again in thanking Dr. von Eschenbach.

[Applause.]

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