The following is a first hand account by Dr. Bret Williams of the Third Annual International Symposium on Malignant Mesothelioma, held by the Mesothelioma Applied Research Foundation (MARF).  The Symposium was held in Chicago, Illinois this October 20 – 21, 2006. 

Dr. Williams is a mesothelioma survivor, who was diagnosed in March of 2003.  Click here to review Dr. Williams' medical history.

Chris Hahn looks like a Californian.  Square jawed, with the slim build of a fashion  model, his blue eyes flash as he speaks earnestly about the Mesothelioma Research Foundation, now the preferred name of the organization known as MARF. 

No one knows what MARF means, really, he explains.  We need to reach more of the public, educate them about meso.

Meso is another favored neologism.  People can’t even say mesothelioma correctly, explained Ann, a board member and professional fundraiser from Texas.  She tilts her head slightly and smiles when she talks, and I see how her easy way with people helps her ask.

The venue is Shula’s steak house in the Sheraton, where we are meeting for two days of scientific presentations and lay discussions.  The International Mesothelioma Interest Group, a more traditional group of scientists and doctors, will be holding sessions next door to ours, and a number of experts will speak to both crowds.  The Meso Research Foundation meeting includes many patients and a greater number of caregivers in addition to professionals, an interesting and stimulating mixture.

Tonights dinner brings together folks interested in helping the Meso Research Foundation with staff.  Those who work for the Foundation are upbeat and smart, discussing not only revised terminology, but also various ways to raise funds and promote meso as a national priority.  Interspersed are a number of folks with heavy burdens of disease and loss.  Ann lost a brother to meso, Hannah and Burt’s son died in his early thirties; Kristen, a slender young volunteer, looks way too young to be a widow.  Laura, who also lost her husband to meso, recognizes me from Washington before I spot her.

Pat and Richard Archer from Alabama are here, very much the good hearted southern folks I expected, and Richard tells me about being a machinist helping to assemble asbestos parts; more than thirty men who worked for his employers have died of asbestos related disease.

David Rice, a young thoracic surgeon from M.D. Anderson, describes their current treatment protocol and explains to me why IMRT can still cause collateral damage to healthy tissue in spite of its greater ability to focus radiation on areas of interest.

I wind up sitting among Meso Research Foundation staff, and I enjoy their  lively conversation and banter.  The waiter brings enormous steaks, very good but much too large for one person to eat.  I grow weary and become the first to leave.

A good group, a good place to be.  More later.

Bret

P.S. -- distortions of fact or mistakes are entirely my fault.

Day One

Registration at 7:30 (6:30 EST), an ungodly hour to get up and shiver outside into a cab.  (Note to self:  Reserve early so you can stay at hotel where meeting is held.)  I greet a few folks from last nights dinner, sit close to the front, greet Linda R with a hug, and meet a few others sitting nearby:  Marion, Elwood, and Sietie, who are originally from Rhodesia.

The first presentations include speakers from Australia and Egypt, emphasizing the global nature of asbestos related disease.  A mining town in Western Australia called Wittenboom (or something similar) sounds eerily like Libby, Montana.

Harvey Pass moderated a discussion about diagnostic markers.  This is important; several proteins found in blood vary with disease activity and show promise both for screening high risk populations and for signaling recurrence in patients with known disease.  Bruce Robinson from Australia gave a particularly good talk.  The Mesomark test now is available there; in the U.S. only investigationally. Harvey has an ongoing study to explore biomarkers further, and Brad Black in Libby is following levels in folks there.

Raja Flores, a thoracic surgeon from Sloan Kettering, then gave a very good talk on imaging.  He included some gross pathology slides that caused many to look away (not me, I’ve been desensitized.)  The CT scan remains the most useful test for diagnosis, but PET scanning is important for assessing disease activity, especially looking for spread of the tumor into the mediastinum (between the lungs) or outside the chest.  No surgeon wants to begin an operation, then find out that the tumor cannot be removed.  He had some term for this that I forget:  it wasn’t “cut and run” but that was the general drift.

The next session was tough sledding for the non-physicians in the crowd, largely a discussion of cellular metabolism and various active molecules (both on the surface of cells and inside them) that may turn out to be good targets for therapy.  I saw eyes glaze over. We have been reading abstracts about such things for some time, though, and a few are becoming very familiar.  VEGF, for example, is a blood vessel growth factor that is expressed in meso more than any other tumor.  Drugs that inhibit VEGF include Avastin, an antibody that is now being tested in combination with chemotherapy; the results of this trial are not yet available but will be soon.

Another important area of research has to do with “epigenetics,” the study of how various genes are turned on or off by intracellular signals.  This is an immensely complex issue, but progress is clearly being made.  Cancer cells do this differently than normal cells, giving us another avenue to explore for treatment.

Michele Carbone is, first of all, clearly a man and pronounces his first name “mikela.”  He left Chicago for Hawaii several years ago, and he began his talk by suggesting we hold the next symposium there.  Many in attendance were clearly interested.

He then spoke at length about a village in Turkey where whole families have died of meso.  Residents of so-called ‘houses of death’, built of asbestos blocks, were particularly vulnerable. Michele and his collaborators persuaded the Turkish government to build a new village to house the families safely.  I could not help but compare the response of our government to theirs.  In a similar context, Nicholas Vogelzang summarized the prevailing attitude of our elected representatives:  “They don’t value life; they just don’t value life.”

Having seriously run over his allotted time, Michele then very rapidly presented some astonishing data linking SV40, the monkey virus that may have contaminated our polio vaccine, with the surge of meso incidence in the last part of the twentieth century.  His laboratory showed an enormous effect of SV40 exposure on the development of tumors in mice.  “Someone else’s lab needs to confirm this,” I thought, knowing that others have scoffed at the notion. Time will tell.

Now I confess that I took a break, leaving the meeting for Manny’s Cafe and Deli, home of the best corned beef sandwich in the world. I shanghaied Laura and the young lady next to her, Stephanie, who left her two pre-teen kids with her husband in north Texas.

Stephanie has had peritoneal meso for five or six years and is doing great.  She seemed delighted at the type of restaurant Manny’s turned out to be, basically a dive with a long buffet of comfort food and a large crowd moving quickly down the line.  “My mother would love this place,” she said.  I expect she thought I was taking them to a nice place.  I can do nice restaurants, but they’re not really my style.

To my dismay, just after learning about her diagnosis I found that we missed the panel discussion on peritoneal meso.  I was mortified, but Stephanie had already spoken with two of the participants and wasn’t worried about missing what they had to say.  One thing that became clear to me over the next 36 hours is that people with peritoneal disease are doing much, much better these days.

Drs Pass and Flores discussed surgical techniques, also much improved.  Harvey noted that pleurectomy and decortication, the procedure in which the tumor is basically peeled off both the chest lining and the lung, appears to improve survival in meso just as much as the more radical extrapleural pneumonectomy, or EPP.  There are advantages to both operations, and he now often begins operating without firm commitment to either, deciding based on what he finds.

Again a series of gross-out pictures are shown, these of surgery in progress.  Neither man said the obvious: “These operations are extremely difficult to perform.”  The vital organs in the chest are packed together like subway passengers, and they are skirted, manipulated, and delicately separated through an opening about the size of your hand.  This may take six hours or more, no relaxing, no looking away, very little stray thought.  These guys have to be artists, scholars, and generals all rolled into one. (Note to self:  No more surgeon jokes.)

We hear about a variety of chemo regimens tested in the U.K., then the fellow who was to discuss Alimta turned out not to be in Chicago. A Dutch fellow spoke about a mouse model for future meso research and a planned study of thalidomide.  Dr Vogelzang was not at first clear about who the presenter was, then suggested that doctors from the Netherlands all look similar.  Works for me.

A ceremony of remembrance followed, where we each wrote thoughts on a smooth rock and built a rock garden under long strips bearing the names of fallen meso warriors.  Three people gave stirring speeches about loss, hope, and community.  Most of us left quietly, lost in thought and emotion.

We returned in the evening for a gala dinner, some folks dressed up.  I got to sit next to Nate and Hope Katz, and we discussed how our lives had changed radically.  Nate expected to stay in the furniture business until “dragged out of the building,” but as we know, life sometimes turns on a dime.  He does not complain, stressing that he feels entirely well except for some mild fatigue and a persistent cough.  Hope is equally positive, a devoted and vigilant ally.

Jordan Zevon and his musical partner Jordan Summers (I think) were also at our table.  After dinner they performed.  Jordan sings better than his father, and the short set was well received.  For an encore, they did a song to which Jordan totally forgot the words.  Didn’t seem to bother him at all, and we all laughed along with him.  So he finished with “Werewolves of London,” one of his father’s standards that most of us knew well.

A few of us met in the coffee shop after dinner.  Some poor guy sitting nearby was drafted into taking pictures with about nine different cameras.  I think everyone but me had one.  I understand they will be posted.

Long day.  More to follow (though likely in much less detail.)

P.S. Somehow I failed to mention the gracious and welcoming Jill Wayne in my description of the previous nights dinner.  I gather she has taken over much of Chris Hahn’s administrative burden at the Meso Research Foundation.

Day Two

“Show me the money!” says Cuba Gooding in the movie Jerry McGuire, playing a professional athlete bargaining with his agent.  This morning we saw the money.  Research financed by the Meso Research Foundation is making a difference.  The first session was what I had most looked forward to: a compendium of promising new treatments and important advances in basic science.

I am not able to cover all that was said.  I will try instead to deal with a few reports in some detail, focusing on issues that I feel are extremely important to all of us.

First, an explanation of clinical trials.  Our best interest may not be served by participating in a trial, but we at least owe it to future victims to consider doing so.  There will be little progress in treatment unless we do.  The rules of the game doubtless differ from country to country, but I suspect the process is similar around the world.  In the United States, this is how it works:

Once a treatment looks good in so-called ‘preclinical’ studies, usually performed on mice, investigators apply for funding to conduct a Phase One trial with humans, enrolling a small number of patients to determine if an experimental treatment is safe.  What they are testing may look promising, but this is not the outcome of interest, and in fact to ask the question (as I did)  “what proportion of patients benefited?” is beside the point.  A Phase One trial establishes safety.  Obviously if patients appear to benefit, then funding for the next step is easier to come by, but there is already good reason to expect a treatment effect or the initial trial would not have been done.

If you join a Phase One trial, you definitely receive the treatment of interest (there is no placebo or control group), and you obtain free, high quality medical care during your participation.  In addition, Dr. Nick Vogelzang pointed out that you may reasonably apply for compassionate use of an experimental treatment at the end of a Phase One trial (i.e., you can try to get added on as a patient with some knowledge that the treatment appears promising.) For those of us who are keenly interested in trying something new, this may be an attractive option.

Phase Two trials go a step further, increasing the treatment and looking for clear efficacy, again enrolling small numbers.  To establish that a treatment works, a control group is needed; this means that some patients will receive the new treatment, and others will receive placebo or standard treatment.

You will still receive free care and medication for participating in a Phase Two or Three trial, but you will not know for sure if you are getting the new treatment or the current standard.  You will be ‘randomized’ to one or the other, and until the end of the trial the clinicians treating you will also be ignorant of which treatment you receive.  This is called a ‘double blind’ since neither patient nor doctor knows and is meant to keep the investigators’ conclusions from being influenced by hope, expectations, or financial interest.

Assume that a new treatment appears to be effective, and that no horrific side effects have shown up in either Phase One or Two studies.  A Phase Three trial may then be done, enrolling large numbers of patients to definitively demonstrate whether or not the new treatment offers any advantage over standard treatment. Especially for a rare disease like meso, these larger trials typically involve collaboration between multiple centers, requiring lots of palaver, arguments between experts about protocol, and considerable travel and administrative expense.  A successful Phase Three trial is expected to result in FDA endorsement.

Taking a new drug through all these steps requires time, patience, and a whole lot of money.  Why, you might well ask, should a pharmaceutical company fund this effort for a measly 3,000 new meso patients per year?  Good question.  The answer is that because meso is rapidly fatal and treatment still sucks, the FDA is more lenient in its oversight.  In a process originally developed for new AIDS drugs, there is a ‘fast track’ system that can speed up getting a promising drug on the market.  And once the FDA issues an indication for a drug, it can more easily be tested and used for treatment of other cancers.

In similar fashion, drugs that have been approved for use against other cancers (e.g. Avastin) can easily then be tried on meso.  These two routes are likely to help us get new drugs tested and approved in spite of how rare meso is.

The group from Penn opened the morning with a presentation of gene therapy, followed by a version of the above discussion.  Before we were brought down by the clinical trial information, the eyes of meso patients and their caregivers around the room lit up with hope.  Dr. Dan Sterman spoke about inserting a gene that causes  cell death into meso tissue through a miniature chest tube, an amazing feat only recently made possible.   Several patients responded dramatically: one who has received no other treatment is entirely stable seven years later.

All of us patients were thinking “I wonder if I can get this treatment.”  My hopes were dashed when Hope asked if patients might be eligible for this treatment after having a pneumonectomy.  “No. Too risky,” was the gist of his reply (he was more diplomatic of course.)

I expect most of us meso patients look at risk somewhat differently.  The risk of doing nothing is considerable.

Others discussed immunotherapy, attempts to make the body attack the tumor.  Conventional wisdom has it that cancerous cells develop in many if not all individuals but are destroyed by our bodies’ natural defenses.  Attempts to rev up the immune system to attack tumor cells have long been promising but have never quite done the trick.  Improved techniques may yet prove successful.

Hedy Kindler gave a good overview of cellular processes that characterize good targets for meso treatment.  At one point she showed a very busy slide representing a cancer cell, with numerous different icons representing cellular receptors and surface proteins and a spaghetti snarl of metabolic process arrows pointing from various intracellular proteins to others. “This is an extremely simplified view of a cell, with some of the pathways we think are important,” she intoned.  Some chuckled, some scoped out the exits.

Basic science presentations were difficult for the crowd but none the less impressive.  Dr. Vogelzang felt compelled to translate for one shy, asian presenter.  The efforts he presented were indeed impressive.  Using a microchip capable of identifying proteins, he and his colleagues developed a library of about 100 million protein molecules found on the surface of meso cells, then subtracted those found on nonmalignant cells.  They then characterized the ones that moved quickly from the surface into the inner cell, where transporting a metabolic poison, gene, or gene modulator might selectively kill the tumor.  This type of work may eventually lead to more effective treatment.

At lunch we sat with scientists here for the International Mesothelioma Interest Group.  Our table included Dr. Paul Sugarbaker, an expert in peritoneal meso, who provided some very helpful advice.  I also spoke with a very nice Japanese presenter, who informed me that asbestos use had recently been banned in his country.  The keynote speaker was Senator Dick Durban from Illinois, who spoke movingly about his support for our cause.

I should mention the two speakers from the local Asbestos Worker’s Union, present both at lunch today and at last night’s dinner.  One tall, one short, they traded off describing close friends and contacts they have lost.  The language they used was classic Chicago dialect (as if to agree with efforts to substitute “meso” for the full name of the illness, one repeatedly said “mesothemiola”.  Their stories were sadly similar to ones we have heard too often, and told ourselves.

Much of the research presented at this conference was funded by the Meso Research Foundation.  In fact , as we learned in Chris Hahn’s closing presentation on advocacy  the total amount of government research funds devoted to meso research is just a bit more than MRF’s annual outlay.  For each dollar spent on research per meso victim, we devote 8 research dollars for each leukemia death, 9 for each prostate cancer fatality, and 12 for each woman who dies of breast cancer.

I draw two conclusions:  1) we should advocate for more federal funding of meso research; and 2) those of us who are able should support the foundation formerly known as MARF.

Hope to see many of you at next year’s conference!

Bret

P.S. My lovely wife,  who is approximately one thousand times as sensitive as I, informs me that I should not mention people in email correspondence without their express permission.  I’m afraid that I do this all the time.  I have no doubt that I have misrepresented what certain people have said, hopefully in trivial ways, but I sincerely hope that I have offended no one, and that if I have that he or she will forgive me.