Cancer

I recently ran across this quote from Mithat Gönen of Memorial Sloan-Kettering Cancer Center:

While there are certainly some at other centers, the bulk of applied Bayesian clinical trial design in this country is largely confined to a single zip code.

from “Bayesian clinical trials: no more excuses,” Clinical Trials 2009; 6; 203.

The zip code Gönen alludes to is 77030, the zip code of M. D. Anderson Cancer Center. I can’t say how much activity there is elsewhere, but certainly we design and conduct a lot of Bayesian clinical trials at MDACC.

Related posts:

Cartoon guide to cancer research
Stopping trials of ineffective drugs sooner
Three ways of tuning an adaptively randomized clinical trial
Population drift

Seth Godin has a blog post this morning in which he says

Smoking a pack a day for twenty years is a great way to be sure you’ll die early.

The point of his post was not the dangers of smoking. His point was that “What we do in the long run, over time, drip by drip” matters more than what we do sporadically and I certainly agree. But I disagree with Seth’s comment on smoking.

Smoking certainly cuts your life short on average. But smoking is like playing Russian roulette: Most of the time, you’re OK. Most smokers do not get lung cancer. Smoking does not ensure that you’ll die early. And that may be why smokers ignore warnings. They can point to plenty of fellow smokers who were not killed by smoking. For example, if I wanted to smoke I could point out that my parents smoked and did not die of smoking-related causes. (Another smoker in my family, however, did die of lung cancer.)

People are most strongly motivated by consequences that are immediate and certain. Given a choice between the certain pleasure of enjoying a cigarette now versus a risk of lung cancer years from now, smokers choose the former.

It’s not very effective to tell someone, especially someone young, that if they smoke they will get lung cancer. For one thing, it’s not true: they probably will not get lung cancer. But they do increase their chances of cancer, and even more so their chances of emphysema, heart disease, etc. Still, those are probabilities of future events. Teenagers may be more motivated by the thought of their fingernails turning yellow or their clothes stinking.

Update: I want to be clear that I’m not defending smoking. I couldn’t wait to move out of the smoke-filled house I grew up in. Nor am I trying to down-play the health risks of smoking. The harmful effects are extraordinary well established. As Fletcher Knebel said back in 1961, smoking is the leading cause of statistics. Half a century later we’re still spending money on studies to confirm what we already know.

Related posts:

Cartoon guide to cancer research
Nearly everyone is above average

The traditional approach to cancer treatment has been to try to eradicate tumors. Eliminating a tumor is better than shrinking a tumor, so this approach makes sense. But if you try to eradicate the tumor and fail, you may leave the patient worse off. If you kill 90% of a tumor with some treatment but leave 10%, the remaining 10% is resistant to that treatment. You may have made the tumor more deadly by removing the weaker portions that were suppressing its growth. This explains why cancer treatments sometimes appear to be quite successful, dramatically reducing the size of tumors, without improving survival.

Sometimes one treatment will shrink a tumor as much as possible as a prelude to another treatment, such as shrinking a tumor with chemotherapy prior to surgery. But if only one treatment is being used, the situation may be like the old saying that you don’t want to wound the king. If you’re going try to kill the king, you’d better succeed.

In a recent interview on the Nature podcast, Robert Gatenby of Moffitt Cancer Center advocates an alternative approach, treating cancer as a chronic disease. Instead of killing as much of a tumor as possible, it may be better to kill as little of tumor as necessary to keep it under control. Patients would continue to take anti-cancer treatments for the rest of their lives, just as patients with heart disease or diabetes take medication indefinitely.

Related post:
Repairing tumors

The most recent Nature podcast (21 May 2009) has a news story about Down’s syndrome and cancer. Most types of cancer are much less common among people with Down’s syndrome. Since Down’s syndrome is caused by an extra copy of chromosome 21, researchers naturally want to know whether a gene on that chromosome is responsible for the reduced incidence of cancer. The podcast interviews researchers from two promising studies of candidate genes.

Here is the abstract of the medical paper discussed on the podcast.

Related post: Cartoon guide to cancer research

The latest episode of the Science and the Sea podcast explains how a protein that gives a certain species of jellyfish a faint glow is useful in research into cancer and other diseases.

Related posts:

Cartoon guide to cancer research
Naked mole rats and cancer
How to treat a stingray wound

Everybody thinks Dilbert is about their job. But this cartoon really is about my job. It does a remarkably good job of summarizing what it’s like to work in cancer research.

Related posts on cancer research

Before I started working for a cancer center, I was not aware of the tension between science and medicine. Popular perception is that the two go together hand and glove, but that’s not always true.

Physicians are trained to use their subjective judgment and to be decisive. And for good reason: making a fairly good decision quickly is often better than making the best decision eventually. But scientists must be tentative, withhold judgment, and follow protocols.

Sometimes physician-scientists can reconcile their two roles, but sometimes they have to choose to wear one hat or the other at different times.

The physician-scientist tension is just one facet of the constant tension between treating each patient effectively and learning how to treat future patients more effectively. Sometimes the interests of current patients and future patients coincide completely, but not always.

This ethical tension is part of what makes biostatistics a separate field of statistics. In manufacturing, for example, you don’t need to balance the interests of current light bulbs and future light bulbs. If you need to destroy 1,000 light bulbs to find out how to make better bulbs in the future, no big deal. But different rules apply when experimenting on people. Clinical trials will often use statistical designs that sacrifice some statistical power in order to protect the people participating in the trial. Ethical constraints make biostatistics interesting.

When I hear of naked mole rats, I think of Rufus, the animated character from Kim Possible.

But it turns out the real rodents might be useful in cancer research. According to a recent 60-Second Science podcast, naked mole rats live in low-oxygen environments. The core of large tumors is also a low-oxygen environment, and so maybe studying naked mole rats can tell us something about cancer. So far researchers have found three genes in common between naked mole rats and cancer cells.

FermiScan, an Austrailian company, is developing a screen for breast cancer that analyzes a small hair sample.

Listen to Moira Gunn’s interview with David Young from FermiScan.

Show notes | mp3

FlowingData posted this graph showing changes to the DNA of a breast cancer cell.

See the original post Researchers map chaos inside cancer cell for details.

CaringBridge offers “free, personalized websites that support and connect loved ones during critical illness, treatment and recovery.” The site is sponsored by donors, not advertising.

When he was diagnosed with cancer four years ago, a friend of mine set up a password-protected web page to let us know the latest updates on his treatment and diagnosis. I appreciated his doing this. He could easily set up his own site, but not everyone knows how to do that. CaringBridge lets people who are not as technically inclined set up their own site. Patients can upload photos, exchange messages with friends, etc. About 100,000 families have set up web sites through CaringBridge so far.

Chemotherapy harms cancer cells as well as normal cells. Chemotherapy is designed to be more harmful to cancer cells than to normal cells, but the damage to normal cells can be brutal.

New studies suggest that fasting prior to receiving chemotherapy may reduce the number of normal cells harmed by the treatment. Fasting may put normal cells in a defensive mode that increases their resistance to chemical attack.

A gene therapy developed at M. D. Anderson Cancer Center for head and neck cancer is the first such treatment to succeed in a phase III trial. See the press release for more details.

(Phase III studies are large, multi-institutional studies required for regulatory approval of new drugs.)

Imagine this conversation with your doctor:

Your poor tumor. It has a chaotic blood supply. Parts of it get too much blood, other parts too little. We’re going to give you a drug to improve your tumor’s blood supply, making it healthier.

Before you run screaming from your doctor’s office, see if there’s a copy of the January 2008 issue of Scientific American in the waiting room. If there is, read the article Taming Vessels to Treat Cancer by Rakesh Jain.

Just as the cells in a tumor are abnormal and growing out of control, so are the blood vessels that feed the tumor. This lack of proper infrastructure inhibits the tumor’s growth, but it also makes it difficult to deliver chemotherapy to the tumor. This lead to the radical idea to make the tumors healthier in preparation for killing them.

So how would you go about improving a tumor’s circulatory system? By administering a drug that was designed to attack tumor vessels!

A new class of cancer drugs, antiangiogenic agents, has been designed to attack tumors by cutting off their blood supply. These agents haven’t been a complete success. Experience with one such agent, Avastin, shows that while it shuts down some of the blood vessels in tumors, it may make the remaining tumor vessels healthier. That’s bad news if you’re treating patients with Avastin alone. But when used in combination with chemotherapy, it’s just what people like Dr. Jain were looking for: a way to normalize the blood flow in a tumor in order to make it more vulnerable to chemotherapy.

More information, including videos, is available at the web site of Dr. Jain’s lab.