IMAGING PANEL SUMMARY by Mathew Freedman, MD

SLIDES & TRANSCRIPTS
Wednesday, June 20

IMAGING PANEL SUMMARY

Matthew Freedman, MD

Slide 1: Lesions 10 mm or Smaller

DR. FREEDMAN: This is not going to be three slides, but it is not a large number of slides.

There was a lot to cover and the first thing has to do with a question asked by the radiotherapists which is can we classify with sufficient accuracy based purely on radiographic and non-biopsy criteria that something has a high enough probability of being cancer that you can treat without biopsy. If we are looking at lesions 10 millimeters or smaller and we demand a 90 percent PPV we are not there yet for a single point of time, and we are not quite there yet for serial studies not including biopsy.

If you look at the curve on the chart you will see that if it meets radiographic criteria for being malignant, the main one being growth and something about structure, malignancy is likely, that is not absolute, and there still will be inflammatory lesions there.
If we call something benign, it is likely to be benign with a very high probability, but we cannot yet reach that goal that the radiation oncologists have asked us for.

Slide 2: Research Recommendations

In terms of research recommendations, the first is that there should be enhanced imaging research components included in clinical and preclinical trials whether these are animal studies in selected cases, we can do serial respiratorcated(?) lung imaging in live mice at the moment or human imaging, but it should be incorporated at the planning stage as it is where I am now where I meet with the SPORE group as we develop new projects.

Slide 3: CT Screening Technique

In terms of CT screening there is a need for some standardization of methods both for acquisition and measurement of lesion size. We expect that there will be a need for an MPQSA. That is mammography quality standards act type regulation of quality, and there is a need for the development and validation of new vogue radiation dose methods which are now being just initiated at several sites.

Slide 4: Computer Methods, Recommendation

In terms of the computer methods the recommendations are No. 1, very important carefully assembled and documented database. This has to be a continuing effort because we know the technology will evolve dramatically over the next 5 years. It has to involve biopsy proof and proof of location is very important for this, and we have to pay special attention to the non-solid nodules or so-called "GGOs," and two questions, do we know enough about the natural history of these for them to be used as a surrogate end point in prevention studies? I would suggest we only know about the ones that have grown not the ones that have not grown, and so, I think that the oncologists may be pushing that further than we now have data to support.
Second, there are probably various causes for those that do not grow. How can we tell which ones are the cancer precursor group?

Slide 5: Computer Methods, Recommendations (cont.)

Third, there is a need for algorithm development and validation both for the machine algorithms that provide measurement and characterization but, also, for the care algorithms. What do we do when we find a nodule of a certain size? What recommendation do we make? That needs to be validated based on lesion and patient characteristics and a follow-up of a large number of lesions. We have ideas as to what this is. We don't have scientific knowledge for it.

We need validation of the reliability of measurements in vivo and in vitro, validated across machine types and manufacturers and validated across image acquisition methods so that if someone has a study in one center and then in another center we need to know what that means and how we can use that.

Slide 6: Contrast Enhanced CT +

In terms of contrast enhanced CT these previous experiments should be restudied with the new high-resolution CT methods. They need computer analysis applied to them for the image pattern, the degree of enhancement. It should be incorporated with data from other computer analysis algorithms based on the individual nodule characteristics, and there is validity in looking at some of the physiologic characteristics that may give us additional information about these lesions, and since we can detect COPD with the physiologic measurements the risk factors of an individual patient.

Slide 7: PET/SPECT

.In terms of PET and SPECT getting nuclear medicine studies we need machine improvement so we can detect smaller lesions. One of the ways this may be done is with respiratory correction or control.
We need new tracer development work for greater specificity, that is labeling the tumor rather than simply glucose metabolism, and we need methods of validating the smaller lesions specifically 5 to 10 and 10 to 15 millimeter size measurements.

Slide 8: Transthoracic Biopsy

The transthoracic biopsy is very important, improved needle design is of critical importance here. It is very difficult working with the current needs that are not optimal for this clinical need. We need methods to make this technique more widely available including training courses. We think that robotic methods, particularly image controlled robotic assistance will be very helpful in disseminating this, and we need intervention of simulators, mechanical computer simulators to train people in how to do this off of patients before they start doing this on patients.

Slide 9: Thermal Ablation Methods

In terms of thermal ablation methods we need to define the potential roles for this. Is it similar to radiosurgery? If so, we will need similar validation methods.

Is it useful postradiotherapy for local recurrence? We need to validate it in the lung post-radiation treatment to know that this is safe.

Should it be combined with adjuvant therapy? These are serious questions. The technique is very promising. It is very early. It warrants continued research and validation in animal models.

Thank you.

Discussion--No Slides Available

DR. BUNN: I have a comment. Hopefully this is going on the Internet, okay, and you just asked about 20 at least questions that are incredibly important, and I think that you ought to put in there that patients should not have any of these tests outside of a clinical trial, but patients should be encouraged to be entering on clinical trials because what is going to happen is if they are not on a clinical trial we are not going to have the answers to your questions, okay, and you are going to have patients backing up the doors getting these needle biopsies. The Davids of the world are going to be putting in needles in gazillions of lesions and no one is going to learn anything, okay, and so if patients in America are just going willy nilly and getting spiral CT scans so some doctor can make some money, we are just not going to have the answers to these questions, and I really think you should have some kind of a statement about saying that when this is done it should be done on a clinical trial.

DR. FREEDMAN: I agree with you completely.
Any other questions or comments?

DR. SAXMAN: Would anyone else like to make any other comments or clarifications?

Would you like to prioritize any of the diagnostic methods that you have discussed? I guess it is sort of on the same lines Paul was saying, you know, there are lots of suggestions or recommendations. I think you could probably spend several hundreds of millions of dollars doing that. The question I guess is how would you prioritize some of those things given limited resources, particularly the imaging components of these?

DR. FREEDMAN: Obviously this is going to reflect my bias that the area is research and of the people who were on the panel, and we tried to come up with recommendations that meet the needs of the entire field. So, I think that that is something that is very difficult for a small group, and Ed seems to want to answer that.

DR. STAAB: Scott, our group has decided to have a post-conference conference, and that is one of the topics we want to address.

PARTICIPANT: One comment on that though, if this is, still the science thing is about designing clinical trials to move forward, could at least the imaging processing and the CD pieces for clinical trials be something that Ed prioritizes as one of the big things to discuss so that early on there is some standardization and some agreement on how to put these trials together in a way that they can be cross analyzed?

PARTICIPANT: Could I just make one comment on that? It is that one way to immediately take advantage there are several imaging directed trials in place spanning thousands of patients. I mean the PSCO and the LCAP and the ACRE(?) trials, these are in place. What we really have is very good cross collaborations with other groups because as some of those protocols stand and they are running they don't necessarily have direct clinical -- they have clinical suggestions but not necessarily adopted guidelines and it would be a real good way of integrating if right now we built on those because those clinical studies have very good attention to the protocols we are talking about, the standardization and to validation of tools, both some we have seen here and others that are around.

So, that is actually in place at the moment but what may be lost is the clinical management and follow-up being rigorously adhered to in that database.

DR. BUNN: I agree with you. I think we don't need 50 zillion new clinical trials. We need to make the ones that are ongoing expanded and in both numbers and follow-up and biology.

DR. FREEDMAN: If I could just comment on that as someone who is involved in the POCO one there are very severe restrictions on the use of that data. I believe there are similar severe restrictions on the Akron trial for the use of this data until the final data is out. In other words, I have been told by Akron in terms of the digital mammography trial you can have the data 5 years from now for your computer-aided detection and diagnosis systems. For POCO there are similar inhibitory mechanisms for this. So, this is something that the recommendation might be to bring this back to the groups that are running those trials and saying that there has to be access to this data earlier for the kind of things that we want to do.

PARTICIPANT: May I just make a comment on that? On the POCO specimens and data, not outcome data though there are rules for access to that material and to the data that they have now. Yes, they are inhibitory. There is a high bar because this is valuable material, but they are available and people have gotten access to them for research studies.

DR. FREEDMAN: I am aware of those rules. Yes, there are ways to access them. I have been told that the truth data is not available but that may not be true. I may have been misled.

PARTICIPANT: The which data?

DR. FREEDMAN: The truth, in other words what is the actual diagnosis on an individual case.

PARTICIPANT: Right. That may not be.