DR. BAST: It may be a solution, but at least an observation. I don't see the diagnostic imagers around the table today.
Having heard what we did a few minutes ago about biopsies and the difficulty in obtaining those, if there were non-invasive ways accurately to reflect what was actually happening to signaling pathways within cancers that were affecting proliferation and apoptosis -- and those techniques are being now worked out with molecular imaging -- you could do a limited number of biopsies to validate those kinds of imaging markers, and perhaps use that to move more rapidly.
Again, you have got the same geographical problems, because not every institution has PET capability, but eventually these will be moved over to MRI markers, so you could ideally have much more widespread distribution of that kind of monitoring.
Again, there are costs involved, but I wonder if involving diagnostic imaging more integrally in GOG as well as in the SPOREs, and also developing a strategy to develop those markers and perhaps serum surrogate markers, could be a benefit.
DR. OZOLS: It would be nice to cover PET scanning, and I think CMS has done some pilot studies to pay for some PET scans in clinical trials. I don't know how broad that would be applied.
You are absolutely right. These are $2,000 a pop studies. So, if you look at the cost of the study, and if you are talking about multiple PET scans, you are still making it a very expensive trial.
DR. BAST: Again, I think that this has to be done strategically. I think, to speak to your point, things need to be prioritized, and you need to figure out where to start and where it is going, so that trials fit together and it is done collaboratively. If you spread that cost over multiple institutions, it could become more feasible.
DR. COUKOS: I just wanted to comment on what Dr. Ozols said. I guess what we are realizing is that a major limitation in the translation of the SPORE projects is to accrue patients fast enough for these projects.
I wonder, the SPORE is meant to be a translational engine that generates ideas and does these readouts. Perhaps what we really need is a connection to a good, clinical engine that has all the trials.
We end up extending the network to other institutions, but obviously there is a very well-oiled clinical engine that is the GOG.
I wonder whether we could use GOG sites and network to run some of the SPORE generated trials. One way to legalize that is the GOG to give points to those sites that run SPORE trials, and which are not necessarily GOG trials. That could really generate incentive to sites to actually accelerate their pace.
DR. OZOLS: Again, we had this hour discussion with GOG leadership, and that is one of the issues that was raised as a potential solution, to try to increase accrual.
The GOG also has their own menu of phase II trials that are often innovative, that have to do biopsies as well. It is really going to be prioritization, I guess, to getting these studies done in a very timely manner.
MS. GOLDMAN: I keep hearing about the need to accrue patients, and we have members of our advocacy groups who are desperate to go into trials.
I think the advocacy organizations, many times, just have to stumble on available trials, or a company comes to us or an individual investigator, because we have worked with many of you, but there is no regular process. Everybody is willing to do it, but there is no mechanism.
DR. KARLAN: One thing I would respond, something that the Gynecologic Cancer Foundation is now working in collaboration with GOG, will be to put the trials and prioritizing them up on the Women's Cancer Network, the WCN website. So, that will actually act as one clearinghouse and making the knowledge of those trials' eligibility criteria available in the public domain.
That is only a first step. We are trying to cull out the GOG language and placing it in appropriate language for the WCN readership. I hope that will at least be a first step as a pilot, that we could then get beyond just some of the high profile GOG trials.
MS. GOLDMAN: We try to let everybody know what the resources are and we put links, but I think we need to find a more defined way to help to do that. We have got some resources to do some more work on that.
DR. SPRIGGS: There are a couple of dirty little secrets here that nobody is really talking about. One of the dirty little secrets is that the institutions where the grant resources reside are frequently not institutions where there is a huge amount of accrual. If you look at the GOG, a lot of the accrual is happening in the community and not in the academic centers.
The second is that half of these patients are not being seen by gynecologic oncologists, but are being treated by medical oncologists, who frequently have no connection at all with the GOG.
The only cooperating group, the SWOG, which had a GYN committee, no longer has one. ECOG and CALGB have neither the time, the energy, or the interest in creating one. Quite honestly, the accrual is, in part, related to the structure that we already have in place.
MS. SCROGGINS: Another accrual issue is that a lot of individuals are not a part of an advocacy group and aren't touched directly by an advocacy group, no matter how well we try to do our job, or how well we try to outreach.
Often women tell me that no one has ever mentioned a physician, no one has ever mentioned going into a clinical trial.
When I mention a clinical trial or ask them, have they thought about it or try to help them find one, it is the first mention.
So, if we really want to improve accrual, there has got to be a real campaign to make it clear that all of our patients, and all of your patients should be told about them, and given the opportunity, because some people just aren't being told.
Another observation, almost every presenter has mentioned the issue of tissue collection or availability. That seems to be a pivotal central issue that needs to be worked on.
I think a considerable amount of energy needs to be gathered around that, and thinking in terms of a mechanism by which we can assure that there is more consistent collection.
I realize that is a big thing. I know it is not simply, let's say let's collect. I know there are signatures that have to be gotten, and things have to be explained such that people understand why you want to collect tissue and so on.
However, until that is resolved, it seems to me that a lot of the things that we are talking about, we won't even have the tissue to do regardless.
DR. BENBROOK: I think, along with the tissue collection, it is very important to consider development of SOPs, so that we have standardization of the quality of the specimens and the usability of the specimens.
It has been a long learning process in the GOG developing translational research protocols, and Kathleen Darcy, our translational research scientist, has worked very hard to greatly improve the standardization and quality of the specimens that are collected.
I think that this type of SOP is very important, especially when we are trying to get biopsies from the community.
How are people within the community going to collect snap frozen tissues? Unless we can develop everything for paraffin-embedded blocks, we are going to need to have very carefully written and followed protocols, in order to have standardization of specimens so we actually have interpretable results.
MS. KOLKER: I think, since we started, the advocacy community and the research and clinical community started meeting together a number of years ago, thanks to some doors that some of you in the room helped open, the advocacy community has grown and gotten much more sophisticated.
So, at the expense of getting as many answers as there are responders, I would like to ask some of the researchers a question about priorities for the advocacy community.
It seems to me that we have heard about a number of problems around tissue banks, around the issue of biopsies, as new targeted therapies are being studied, lots of concerns around IRBs and streamlining their procedures, particularly when trials are multi-institutional, encouraging cooperation across cancer sites, as we are looking at molecular targets that are common in a variety of cancers, and of course the bridge between -- one just mentioned the bridge between gynecological oncologists and medical oncologists, and there are obviously many more. These are just some that I have heard this morning.
My question is, could the -- is there any advice that you could give to the advocacy community about priorities, because resources are limited, but also a great deal of knowledge has been gained in the last few years.
It strikes me that the advocacy community does not work on all of these, but if we do, it is a tidbit here or a tidbit there, but perhaps there is some way that the advocacy community could come together around a couple of priority cross cutting issues that could help the scientific and research communities move forward.
DR. KARLAN: I think you point out, for everyone again, all of the problems that we are all addressing here today.
Many of them are personal issues, and individualized patient and institution issues that, again, the advocacy community, through your structure, through your outreach, provide an enormous resource.
I think banding together -- you mentioned the word, resources. I think band together with your voice in Washington , get more money devoted to the programs. I mean, that is clearly one way that the advocacy community's voice -- yesterday on the Hill, clearly, each Senator and Congressman Carol and I met with wanted to hear from the advocacy constituents in their own community. So, that ongoing work through We Can and other things, would be great.
In terms of, again, the things we have discussed before, awareness of clinical trials, and the support and education you provide, I think, in terms of over-reaching goals.
You are not going to be able to help us too much with the IRBs. You may serve in your own community, but many of those, the questions with regard to patient biopsies in many of those are so individualized, that I don't know that it is going to be the highest priority for all of your organized efforts.
DR. BECK: I just wanted to address some of these issues. I suspect a number of you remember the RFA for regional translational research centers. Remember those? A show of hands? Anybody? No?
This was a great initiative that was designed to pull together resources in a community to address all of these issues in terms of capturing the patients out in community hospitals who might not ordinarily be on a protocol. It was designed to bring together translational science and the clinical protocols.
This was a great initiative, and those of us in Chicago, the University of Illinois, the University of Chicago, Northwestern, a couple of other places, got together and put one of these applications in.
It turned out that the NCI decided to take back -- was re-thinking how it was going to, in fact, prioritize, and decided it wasn't going to fund these programs.
In fact, these programs, it seemed to me -- so, there was not even a study section. So, it seems to me that this kind of initiative, though, can work, perhaps not nationally, but in regional areas, to try this out.
We had already dealt with IRB issues, and put in place a mechanism -- we had already begun this before, but put in place a mechanism to try to get a regional IRB -- it is not completely solved, we have still got problems -- and then intellectual property issues also.
We thought we were going ahead pretty well with this, and I suspect a lot of the other institutions who applied for these were doing the exact same things. So, maybe community-based efforts on a local level might help to be able to address some of these issues.
DR. QUALMAN: On tissue banks, I have two comments. The first one is, when it comes to procurement of tissue for research efforts for gynecologic patients, I think the single biggest issue is local logistics and availability of resources.
That is why these community hospitals that obtain tissue struggle. Do they have a centrifuge? Do they have the right blood tubes to draw the blood in the proper container? Do they have availability of liquid nitrogen?
I think the GOG has been really the leader amongst the Cooperative Groups in educating their data managers and having handling sessions for specimens, containers, et cetera, at their meetings, and developing standardized SOPs.
Although that will solve some of the problem, ultimately there are just basically some physical features and equipment that are needed in all places, that are common across the board that, until they get them, this problem won't be solved, despite what we can do, and that is a matter of money. That is my first comment.
My second comment, which is more positive, is that there are already ongoing collaborative efforts between the ovarian SPOREs and the GOG tissue bank.
We have, with the UAB SPORE, traded tissues to build effective tissue microarrays. So, there have been some grass roots efforts to make that happen already.
DR. BOWTELL: Just as a follow on to that, is there an audit of the availability of tissues somewhere easily accessible for the SPOREs and GOG, so that we can get a sense of what fresh frozen, paraffins and TMAs are available?
DR. BENBROOK: I know there is with the GOG. Would you like to address that?
DR. QUALMAN: There is an audit, or there is an inventory that is available, a couple of websites that the NCI has put together and on the GOG website.
It is a fairly gross audit in terms of X numbers of various kinds of cancer. If you really want to get into the details of subtypes of cancer, you have to contact us and we can run it for you.
DR. MANNEL: I think one of the examples of the GOG willing to put a lot of resources and energy and effort into translational research is GOG-210, and that is a very heavily translational research project looking at endometrial cancer.
The amount of funds that are being applied to that are substantially higher than any tissue acquisition studies we have in ovarian cancer.
I think if we truly want the large translational commitment of the GOG, and the large resources it can bring to bear, it once again comes to a prioritization of resources.
I think the network has shown it will get tissue, it will get high quality tissue, but the current reimbursement for ovarian tumor is remarkably low, unless it is tied directly to a treatment trial.
So, if you want a standalone, translational research trial, which perhaps you need, particularly in early-stage ovarian cancer, that is a great example. It would be great to have early-stage ovarian cancer tissue, and it would be, but there is no survival trial that you can design for early-stage ovarian cancer, because survival is too high at the current time.
That doesn't mean there aren't great molecular questions that can't be asked, but then the GOG is not designed to necessarily provide resources to ask those molecular questions.
So, if you want to get off the mark here, we may need to reassess what some of our endpoints are. Now, that has been brought up several times. Molecular endpoints may not translate into survival advantage for some time to come.
DR. SCHILDER: This is to Dr. Beck. If a clinical investigator has a concept, but needs some very focused preclinical data missing to gaps in the protocol, could the experimental committee provide that support, or is he on his own to find a collaborator?
DR. BECK: That is exactly what we are here for. If we don't have the expertise to help you out within the committee, we can help you identify that resource, but that is exactly it. Thank you for the question.
DR. BENBROOK: I am thinking about the NCI subcontract mechanism, where an institution can apply to qualify for performing subcontracts.
It would seem that it might be appropriate for the community hospitals or community docs to actually try and qualify, and apply for something like that, to show that they have the infrastructure, the physical means and the capabilities of collecting tissue, and then actually have some of that money coming from the NCI specifically to support this Intergroup tissue collection and participation in clinical trials.
DR. MINASIAN: I run the Community Clinical Oncology Program. Of the 63 Community Clinical Oncology Programs, at least 15 to 20 are members of the GOG, and would be more than happy to participate in tissue collection studies, if they had the additional resources to do it.
So, as Steve eloquently described, many of them can do it. It is just the logistics at the local level which requires additional dollars.
DR. CIBULL: It is not just the amount of money it takes to collect a given specimen. It is the amount of money it takes to set up an existing infrastructure.
There has to be somebody at the site who is willing and able to collect the tissue, and that person exists whether there is tissue there to collect or not.
I think that it involves quite a bit of money, and I am not sure that focusing on collecting tissue at small centers is the most cost effective way of collecting tissue.
I don't think I would get hung up on that. I think if we were able to access the material that is available at major academic medical centers, we would be doing just fine.
The impediments to that are, again, funding primarily, but also the time and trouble it takes the clinician to participate in those kinds of studies and, quite frankly, the willingness of the patient to participate in those studies.
I think, in a room like this, with the advocates in the room, these are the most highly motivated and informed and intelligent people in the patient community.
Not all patients share their altruistic view of cancer care. In my own institution, many patients have refused to go on trials -- haven't refused to go on trial, but have refused to have their tissue taken, and some of that is cultural.
So, I think it is multifactorial, but personally, I wouldn't get hung up on trying to involve the 50-bed community hospital in supplying ovarian cancer tissue, or even the more sophisticated hospital with no person available as a standard to do that.
MS. SCROGGINS: My question has to do with the point that has just been made, two points. One is, I wanted to know whether there were any ongoing collaborations between some of the major cancer centers and, say, the community health centers and the local docs.
I want to know if there are best practices in terms of maximizing on both services and both sources. Also, if you don't include those -- I am not going to get hung up on including the community health centers in terms of their doing the actual collections, but the populations they serve must be included.
So, that is my issue, and whatever way you do that, whether it is because you are doing something collaboratively or because you are helping with their own infrastructure, the bottom line is, we need to make sure that all people are included.
The issue of recruitment and whether people are willing to have tissue samples taken, one of the big issues, I think, in terms of lots of communities, and particularly people who are not really tied into the advocacy community, is explanations. They want to go why.
If you simply give a form and say, this is what we want to take, this is what we want to do, the more places they have to sign and the more things that they feel they are giving up, the less likely they are to sign.
So, we need to do some PR work to make sure that people understand and are educated to know exactly what it is and why it is important, particularly in those communities that are already leery of the words, clinical trials.
DR. HAMILTON: I actually think that one of the problems with getting tissue is the issue of perceived benefit.
Larry Weisenthal is here, and I am sure he might be able to comment on where the majority of the tissues come from that go to the various drug resistance or drug sensitivity assays.
The last I heard, the various companies that do this, they get thousands of specimens per unit of time, and the reason they are getting them is because community hospitals, by and large, the physicians, I believe, have a perceived benefit of the test. Maybe Larry will say something, because I think if someone thinks they are getting something, they send tissue.
MS. GARDNER-QUADE: On this issue of accrual of patients to studies, as well as wanting to participate in tissue acquisition, wanting to, number one, make the clinician's time more efficient, and also the issue of education to the patient.
I find that oftentimes that interaction time between the clinician and the patient actually could go much more smoothly, when the patient has already had some prior knowledge of studies or trials with tissue acquisition.
They sort of come already, if you will, with some type of background information and knowledge, and actually are more receptive because seeds of thought have already been planted.
A quick and easy place where that can be done is that, at the time when the visit is -- the appointment visit is made, there is a list that we already give to the patient for things that they need to do prior to that consultation visit.
Have your records with you, have old films with you, have your slides with you, et cetera. We can also slip them a FAQ sheet, if you will, just sort of an overall fact sheet introducing the notion of clinical trials, this is an institution that is involved with that, and tissue acquisition.
It could be very short, it could be to the point in language understandable, but at least the point of communication has actually been initiated prior to that critical consultation discussion time with the clinician. Therefore, it may actually improve on patients wanting to be involved in clinical trials, and understanding the need for tissue acquisition and may decrease the amount of time in the consultation and consent process.
DR. BENBROOK: Okay, we are running out of time, and I guess we could have one more comment there. Okay, let's have the answer to Dr. Hamilton's question.
DR. WEISENTHAL: I have been sitting here all morning taking notes about all the problems that people are bringing up.
It is striking how a single technology is kind of the solution to 80 percent of the problems you are talking about here.
Rather than explaining that, what I would like to do is take one minute and propose a very simple clinical trial, and then I will tell you, if that trial is positive, where it will lead.
The very simple clinical trial that I would do, that I think could be completed in six months at minimum cost, perhaps no cost at all, would be as follows, and that is, the goal is to see, with available what I call open source cell culture technologies, is it possible, with a high degree of sensitivity and specificity, to accurately identify platinum resistance.
So, the design of the clinical trial would be this and that is, it would take 60 patients. You would have 30 patients that were previously untreated, that had never had any chemotherapy, and you have 30 patients that meet the definition of platinum resistance.
You biopsy -- as you know, with ovarian cancer, you can quite commonly get a lot of tissue. So, you get tissue from large volume biopsy samples from 30 untreated patients, 30 platinum-resistant patients, and you send those -- you know there are a variety of labs that are doing this in the real world.
You send those specimens on a blinded basis to whatever labs want to participate. So, each lab tests 30 specimens from untreated patients, 30 specimens from patients that meet the definition of platinum resistance.
I can tell you, there is an astonishing difference between them. I am 100 percent certain that, if you sent me 30 blinded specimens from untreated patients, and 30 specimens from platinum-resistant patients, that I would blow you away with the difference in magnitude of that.
Now, once I prove to you that I can do that, that I can identify to your satisfaction, the difference between prior to treatment, between a platinum-resistant ovarian cancer and a platinum-sensitive ovarian cancer, I mean that just opens up a world of opportunity.
In terms of specimen acquisition, you know, I am a little lab, but I am looking at the numbers that you guys are getting in your big groups, and me and my wife, in a year, can do better than you can do in terms of accruing specimens, and we don't have to get any informed consents or anything like that.
We get them from the small community hospitals, also from some of the large community hospitals, like Memorial Sloan-Kettering and Dana-Farber and things like that, occasionally.
The point is that it is getting late and I think what I am going to do is put this in a letter, but I am going to outline all the various things that would flow from just that one simple clinical trial, which could be completed in six months, to just show that, with existing open source technologies, that I could then teach any lab that wanted to do it -- and this is not rocket science, this is not even microarrays, this is reproducible, pretty simple stuff.
So, if you had the ability to test an ovarian cancer and if the only question you could answer is, is this platinum-sensitive or resistance, that would be phenomenally important for the patient, and it would just open up a world of opportunity in all sorts of areas, that I will detail in my letter.
DR. BENBROOK: I would appreciate receiving that letter, because we are working on a white paper. I would like everyone to keep in mind that this is more than just tissue collection.
What we are really going for is collecting specimens associated with the clinical trials, MRI imaging and biomarker specimens that can really help us to identify prospectively what is going on within the treated patient.
So, since we are out of time, I would just like to have one very short, closing, inspirational comment from Susan, who wanted to say something.
MS. BUTLER: I don't know how inspirational it is, but I think it is obvious. Some institutions seem to do an exceptional job of recruiting people for trials. Some institutions don't.
I have yet to come to one of these meetings and see a session devoted to how to do this well. Why? If this is a huge stumbling block -- and it clearly is -- as always, tissue is the issue.
It would seem that either NCI, GOG, anyone might do well to convene a group to develop clear markers for executing clinical trials and recruitment of tissue and the rest of it well.
DR. BENBROOK: Thank you.
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