Summary




SLIDES & TRANSCRIPTS
Wednesday, June 14, 2000

Welcome and Charge for the Meeting
Scott Saxman, MD
Slide 1:

DR. SAXMAN:  The Lung Cancer State of the Science is one part of a pilot project, based on recommendations from the Armitage Committee, to enhance clinical trial design and development.


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Slide 2:

In genitourinary, and lung cancer this includes Concept Evaluation Panels, which were developed to broaden external participation in the review process, and a Cancer Trials Support Unit, which will expand participation in Phase III clinical trials to a larger group of investigators and patients.

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Slide 3:

So the goals of the State of the Science conferences are:  (1) to stimulate and accelerate the development of new clinical interventions for patients with lung cancer in this case; (2) to exploit what we know and what we are learning about the biology of lung cancer for clinical trial development and design; (3) and to begin or to continue to identify the issues that need to be addressed, and the tools that will be necessary in order to fully explore some of these new interventions.

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Slide 4:

There was a recognition for these conferences that achieving these goals would require input from a broad group of investigators, and individuals with a diverse area of interests and expertise, and that other scientific forums did not necessarily include such a broad group of individuals including: medical oncologists, radiation oncologists, biologists, surgeons, imaging radiologists, basic scientists, industry researchers, and individuals from the patient advocacy groups.

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Slide 5:

The first lung cancer State of the Science conference was held in September 1999, and was titled, "Molecular Targets for Therapy in Small Cell Lung Cancer." 

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Slide 6:

There were several things that came out of that conference, but there were two major issues, that were identified.  One was the need for a small cell lung cancer tissue bank.  Many of the investigators, particularly the basic scientists identified this as a significant problem, because small cell is not a surgical disease.  So there is a paucity of tissue available for correlative studies.

So after that meeting we had developed and put together a group of people, including Bill Travis from AFIP, a couple people from the SPORES – Adi Gazdar, and Wilbur Franklin, Henry Tazelar from the Mayo Clinic -- and have begun to develop a cooperative effort by investigators, with funding from CTEP and the SPORE program to put the infrastructure together for a tissue bank.  And then hopefully at some point in the future, begin to start collecting these tissues for use by scientists.

The other issue that was identified was the need to further develop neuropeptide receptor antagonists.  I can't go into a lot of detail about this, but at CTEP we are currently in discussion with a pharmaceutical company that has a couple of these receptor antagonists, and there have been proposals submitted to the RAID program and the SBIR program.  Anyone that is interested in more information about that can speak with Paul Bunn.

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Slide 7:

So why did we choose locally advanced non-small cell lung cancer for the second conference?  I think this is probably fairly obvious to most of the people in this room. But this is a disease where a multimodality approach is clearly important in the treatment, and David Gandara will talk more about that this morning.

The interactions between the tumor biology, the chemotherapy, and radiation therapy are complex, and I think often poorly understood, and need to be explored further.  Evaluating new agents with unique mechanisms of action, I think will require a better appreciation and careful consideration of these interactions.

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Slide 8:

Because of the number of new agents, and these distinctive mechanisms of action, it's going to require utilization of new tools to evaluate the biologic effects of these agents, and I believe new paradigms for clinical trial design will need be developed and utilized.

I think we are finding that our parameters such a maximally tolerated dose and response may not be the most appropriate criteria for decision-making any longer.  And yet, it is not practical, or in my opinion, necessarily desirable to move directly to large scale Phase III testing. So the developmental studies will need to ask and answer scientific questions that will be necessary to make decisions about large-scale testing.

And to address these issues, input will be necessarily from a variety of experts working in a variety of disciplines, and that's why you are all here today. 

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Slide 9:

So this will be the format of the meeting.  We have designed this similarly to the first meeting, building on what we did in September.  There will be a series of morning presentations designed to help highlight some of the important issues in this disease, and to give people an opportunity in this larger forum to discuss what some of those issues are.

Then there will an independent afternoon working session, three breakout groups or working sessions.  There will be two moderators for those sessions. The moderator's job is to help keep the discussion focused and on track.  You should have received several handouts in advance of the meeting to help you also prepare to discuss the relevant issues.  The moderators will also be responsible for presenting a summary of the work group's deliberations on Thursday morning.

For this meeting, slightly different than the last meeting, we have asked four or five people in each working group to give very short 5-7 minute mini-presentations about their work.  The goal here is to help initiate the discussion, to give people a starting point to begin to discuss some of the relevant issues.  I have asked these individuals to keep these presentations short, and I would ask you again this morning to do so, since they are not meant to be summary overviews, but again, a starting point for discussion for the group in general.

The morning presentations and the summary sessions will be made available on a website so that interested individuals can view the proceedings of the meeting.  These working sessions this afternoon, however, will not be recorded.  There will be an individual there to take notes.  The notes will be used exclusively for the moderators to make slides for tomorrow morning's summary presentation.  So the working sessions this afternoon, hopefully you will feel more free, and a little less restrained, because those will not be made available, except as a summary tomorrow morning.

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Slide 10:

So the charge to you as participants is to participate openly in a dialogue that is intended to discuss promising developments or opportunities in research in locally advanced non-small cell lung cancer, and their application to clinical intervention, and to discuss and make recommendations regarding the steps that will be necessary to move novel therapeutic approaches to definitive clinical trials.

And the third goal is to have a little fun with this.  I would hope that you would see this as an opportunity to sit and discuss a topic that is near and dear to your heart.  Almost all of you are doing research specifically in lung cancer, and those of you who aren't, are certainly doing research that has applicability to lung cancer.  So I hope that we set this up so that it's also enjoyable to be able to just sit and discuss these issues with colleagues.

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Slide 11:

Just a very quick word of thanks.  The co-chair for this meeting who has been instrumental in helping me identify individuals in the radiation oncology and radiation biology community is Richard Cumberlin.  Rick is in the Radiation Research Program at the NCI, and is actually going to say a few words in just a moment.

There were many people who helped as part of the planning committee.  The main individuals I have noted here, although there are others I am certain I have not put on this list, and I would like to thank them as well, but Chris Berg, Diane Bronzert, John Hoffman, and Ed Staab from diagnostic imaging, Beverly Meadows and Sheila Taube.  I want to thank all of the speakers in advance who have agreed to give talks this morning, and the working session moderators, who have a difficult job this afternoon and tomorrow morning.

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Slide 12:

Then just again, to sort of reiterate that these meetings represent an ongoing process.  I suspect that we're not going to cure lung cancer over the next day and a half.  But hopefully these meetings will provide us an opportunity to have meaningful discussions and interactions as a community, and to assist us in continuing to identify and move in the right directions.

What I'd like to do now is introduce Dr. Richard Cumberlin, the co-chair for the meeting, who is going to also say a few words of introduction.

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Slide 13:

Welcome and Charge for the Meeting
Richard L. Cumberlin, M.D.
National Cancer Institute

DR. CUMBERLIN:  Thank you, Scott.   I want to thank all of you for coming here and offer a word of explanation as to why there are so many radiation oncologists here at a meeting that is designed to integrate new therapeutic modalities and new agents into the treatment of lung cancer.

The reason is that in the past decade, we have learned a great deal about the mechanism of action in radiation biology, by no means all of it, and as was mentioned before, it is still poorly understood.  But we have learned two things.  Radiation interactions are not limited to the nucleus any longer, and they are no longer limited to double strand breaks.  There are a great number of things that go on when radiation hits a cell, and many of these are in common with the things that happen when chemotherapy hits the cell.

We are learning that many of the mechanisms that radiation therapy introduces can be affected by some of these new agents, perhaps not all of them, but certainly some of them, although you might be surprised that angiogenesis interacts with radiation therapy.  Gene therapy is being used in radiation therapy clinical trials.  Clearly, radiation therapy has a great role to play and a great deal to do with these new agents and new mechanisms.

Radiation therapy, however, is still a locoregional modality.  We have also learned over the past decade that we can increase local control with radiation therapy, and even more so in combination with conventional chemotherapeutic agents.  These do have toxicities, however, and it may be possible to increase local control with these newer agents that have less toxicity, but nevertheless interact on a molecular mechanistic basis to increase the effectiveness of radiation therapy, very possibly increasing the induction of radiation apoptosis B apoptosis being a word that has just come into the radiation biologist’s vocabulary.

Local control can increase cure and I think we are seeing that in the clinical trials coming out now, although we don't purport that if we could get 100% local control we would cure all lung cancers.  It is a worthy goal, to try to increase local control and the effect of radiation therapy as much as possible.

We welcome the interaction with the tumor biologists and medical oncologists in helping to make this happen, hopefully being able to make a dent in advanced lung cancer, which has not been easily cured as of now.   Hopefully we will have a blueprint for the next five years or so as to how we can either improve the outcome of this disease and/or increase our knowledge of what happens, so that five years from now we will have a much better idea of what to do.

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