Tuesday, March 27, 2007

Tony Snow. And a story.

I'm interrupting the gallbladder series for a moment, at the news of Tony Snow's discovered metatstatic colon cancer in his liver. As I said about Elizabeth Edwards a couple of posts back, when famous people get sick, it's an opportunity to learn. If nothing else.

In the case of colon cancer which has spread to the liver, the outlook is not good. On average, survival is in the range of six months (as with all cancers, there are variations in both directions). There are exceptional circumstances, for instance when it appears that only one tumor nodule is growing in the liver, in which case removing it and giving chemotherapy may prolong life. Unfortunately that's rare: in most cases when it's discovered, it's widespread. Response to drugs is usually brief. Some data suggest improved response when the drugs are infused directly into the artery to the liver (in the linked diagram, the images are of experiments in rats. The one on the right is sort of like what happens in humans).

In my practice I had one patient who defied the odds so dramatically that I hesitated to mention him when I talked to others in whom I'd discovered the disease. My desire was to be candid and realistic, but, at least early on, to encourage a trial of treatment. Compared to some, the drugs used for liver metastases of colon cancer are usually well-tolerated. Response is not great overall, but once in a while.... So I'd generally suggest giving it a try, but I didn't want to raise expectations inappropriately.

My patient was in his forties and feeling healthy until he started noticing blood in his stools. It wasn't until he started having frequent cramps that he decided to see his doc, at which point, unsurprisingly, he was found to have a large tumor in his sigmoid colon. His CEA (a blood test related to colon cancer, the usefulness of which in terms of diagnosis and treatment remains controversial) was the highest I've ever seen, consistent with the amount of tumor in his liver. Nevertheless, to prevent impending obstruction, and to stop his bleeding, I operated and removed the tumor. After rapid recovery, I sent him to an oncologist who began chemotherapy. I didn't see the man again at that point, although I got the occasional office note copied from the oncologist, noting dramatic drop in the CEA levels. Eventually the man dropped out of my consciousness.

Until about eight years later, when he accompanied his wife on her appointment to see me for gallbladder surgery (see, maybe I'm not really interrupting the series after all). He looked like a million bucks. Is it wrong to act surprised to see someone alive? "Wow!" I blurted. "How great to see you! Look at you... [I figured you'd be dead by now.]"

In such a dramatic and nearly singular situation, you have to wonder if it was the drugs or if somehow his tumor had mutated in such a way as to allow his immune system to recognize and destroy it. There's no way to know. But, wanting to present a glimmer of hope in terrible circumstances, I did mention this man to subsequent patients. Until there's evidence to the contrary, I'd say, it makes sense to hope for the best while preparing for the worst. That's what I'd tell Tony Snow.

Addendum 3/28: Orac has a post on the subject, in which he says with the addition of anti-blood-vessel-forming therapy the median survival of liver metastases from colon cancer is 20 months, while five-year survival remains uncommon. I'd take his word over mine; he's active in the field, I'm an old guy. Ironically, I've been asked to move my blog to Scienceblogs, where his is. I'm debating with myself if I'm enough of a science guy to belong in the club. Maybe not.


Richard A Schoor MD FACS said...

It is very tuff balancing realistic odds with optomistic hope. Nice piece!
BTW: I read and enjoyed your book, especially the afterword. You are a very good writer.

SeaSpray said...

When I heard the news about Tony Snow today - I thought of you Dr. S. because of what you said the other day about Cancer. You said that when people say it came back (as they said about Tony today)that it really never left. He seems like such a good man and I truly wish him well.

We found out today that our aunt who has been responding well to the chemo/radiation is going to be able to have her breast removed on April 10th. geez - that sounded weird. Just that she was so bad before they couldn't do the surgery and now they can and that is where the CA originated from.

I am glad your patient did so well. it must be awesome to have a job that you get to help save someone's life.

Lynn Price said...

"I object slightly to the notion that her cancer has "returned." It never left."

I know this was from your Edwards thread, but it's germane to Tony Snow as well. I'm confused about this concept because I've heard docs say they can't find any trace of a cancer, leading to the idea that it has, in fact, cease to exist. Are you saying that there are simply too few cells to show up in a blood test, and that the cancer is still there?

Also, what about those whose cancer never returns? Have the cells been eradicated or simply never grew?

Thanks in advance for the education.

Sid Schwab said...

Lynn: you're correct.. In the case of recurrance after being told no tumor can be found, there are not tests able to detect very tiny amounts. Assuming cells spread singly from a primary tumor, it can take years for the cells to multiply (there's the notion of "doubling time," ie the time it takes for the number of cells in a tumor to double, which can vary by months to years) enough to become detectable. In the case of apparent cure, it's probably both: complete eradication in many, or developing some sort of "steady-state" in others. The fact is that some tumors (notably breast and melanoma) may recur furiously as much as twenty or more years after treatment. That's pretty uncommon, by the way; people who've gone that long really don't have much to worry about, statistically speaking. But it suggests that some "cures" don't require complete eradication.

Anonymous said...

Great point. I saw a patient this week with a mass just above the left clavicle which is a metastasis from her breast cancer treated with surgery and chemotherapy 22 years ago. It is apparently the only site of disease. She was stunned to think that her cancer has been present but dormant for so long. Ah, Biology!!!

Greg Pawelski said...

In regards to Orac's comment about anti-blood-vessel-forming therapy, there is a "functional profiling" Microvascular Viability Assay for anti-angiogenesis-related drugs.

A major modification of the DISC (cell death) assay allows for the study of anti-microvascular drug effects of standard and targeted agents. The assay is based upon the principle that microvascular (endothelial and associated) cells are present in tumor cell microclusters obtained from solid tumor specimens. The assay, which has a morphological endpoint, allows for visualization of both tumor and microvascular cells and direct assessment of both anti-tumor and anti-microvascular drug effect. CD31 cytoplasmic staining confirms morphological identification of microcapillary cells in a tumor microcluster.

The principles and methods used in the Microvascularity Viability Assay include: 1. Obtaining a tissue, blood, bone marrow or malignant fluid specimen from an individual cancer patient. 2. Exposing viable tumor cells to anti-neoplastic drugs. 3. Measuring absolute in vitro drug effect. 4. Finding a statistical comparision of in vitro drug effect to an index standard, yielding an individualized pattern of relative drug activity. 5. Information obtained is used to aid in selecting from among otherwise qualified candidate drugs.

This kind of technique exists today and might be very valuable, especially when active chemoagents are limited in a particular disease, giving more credence to testing the tumor first. After all, cutting-edge techniques can often provide superior results over tried-and true methods that have been around for many years.


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