October 22, 2006 - Power Grid

I conducted a couple of difficult funerals this week. No funeral is easy, but each of these involved men in their thirties – the sort of death that’s just not supposed to happen. One man died in a car accident, the other from stomach cancer that was diagnosed only four or five months ago.

Both funerals involved the familiar ritual of family and friends gathering at the funeral home, for what is blandly and euphemistically called “visiting hours.” In my more than 25 years of ordained ministry, I’ve been to more of these gatherings than I could possibly count. It goes with the territory, when you’re in ministry.

There’s not a lot that happens, during visiting hours (or so it would appear, to the untrained eye). After spending a few moments greeting the bereaved family and expressing words of sympathy, most guests simply sit or stand around, sharing small talk with neighbors. It’s one of the few occasions in life when all you have to do is show up.

Over the years, I’ve come to realize there’s a lot more going on during visiting hours. What the eye sees is but the tip of the iceberg.

There’s a new book called Social Intelligence: The New Science of Human Relationships, by Daniel Goleman, that’s been getting a lot of press. I haven’t read it, but from the reviews, it appears to have a lot to say about what goes on behind the scenes in many human interactions.

Based on psychological research, Goleman’s point is that a large portion of our emotional interactions are non-verbal, and take place on a subconscious level. In an October 10th essay in the New York Times, “Friends for Life: An Emerging Biology of Emotional Healing,” Goleman describes his findings:

“Research on the link between relationships and physical health has established that people with rich personal networks – who are married, have close family and friends, are active in social and religious groups – recover more quickly from disease and live longer. But now the emerging field of social neuroscience, the study of how people’s brains entrain as they interact, adds a missing piece to that data.

The most significant finding was the discovery of ‘mirror neurons,’ a widely dispersed class of brain cells that operate like neural WiFi. Mirror neurons track the emotional flow, movement and even intentions of the person we are with, and replicate this sensed state in our own brain by stirring in our brain the same areas active in the other person.”

Goleman reports that some researchers have used language like “the merging of two discrete physiologies into a connected circuit.” They think they’ve found evidence in brain chemistry to prove the existence of such a connection. While the physiology of this brain-to-brain link is highly speculative at this point, there does seem to be some circumstantial evidence that such a link exists: such as one study that asked women volunteers to submit to MRI imaging, while awaiting a mild electrical shock. When one of these experimental subjects waited alone, her anxiety level increased. When a stranger held her hand, her anxiety level was unchanged. Yet, when the woman’s husband held her hand, “she not only felt calm, but her brain circuitry quieted, revealing the biology of emotional rescue.”

No, there’s a lot going on during visiting hours in the funeral home – as people awkwardly mill around, seemingly doing nothing. They may not be consciously aware of it, but they’ve come there that day to plug into the power grid of spiritual and emotional support. By their mere presence in the room, they lend strength to their bereaved family, friends or neighbors.

Centuries ago, the Elizabethan preacher and poet John Donne penned these famous words, as he wondered, during a time of plague, whether the funeral bells from a nearby church might soon be tolling for him:

“No man is an island, entire of itself; every man is a piece of the continent, a part of the main. If a clod be washed away by the sea, Europe is the less, as well as if promontory were, as well as if a manor of thy friend's or of thine own were. Any man's death diminishes me, because I am involved in mankind; and therefore never send to know for whom the bell tolls; it tolls for thee.” ("Meditation XVII," from Devotions Upon Emergent Occasions)

One thing my cancer has taught me is the importance of these connections between people. We can be agents of each other’s healing.

October 11, 2006 - Chemo Brain?

One of the more controversial side-effects of chemotherapy is something called "chemo brain" – experiences of mild confusion, mental fuzziness or loss of memory that occur both during and after chemotherapy. Many doctors deny that chemo brain exists, as a discrete side-effect – seeing it as simply another aspect of the stress, fatigue and general emotional strain that are part of living with cancer. Many chemotherapy veterans, though, aren't so sure.

I can picture several members of the support group at the Cancer Concern Center discussing the subject, at one of the weekly meetings. "Oh, yes," they were saying, nodding their heads vigorously. "Chemo brain is real."

I also have a memory of asking Dr. Lerner about it, as he was briefing me on what side effects to expect, as I began treatment. His reply was that, yes, he'd heard patients use the term, but he hadn't seen anything yet to suggest there's a physical explanation for it. He sounded skeptical, although he didn't categorically rule it out.

Now, there's a new study that suggests that chemo brain is a real phenomenon, that may continue for as long as ten years after treatment. To quote from a Yahoo! News story of October 5, "Chemo Has Long-Term Impact on Brain Function" (based on a Reuters press release):

"The researchers, from the University of California, Los Angeles, found that women who had undergone chemotherapy five to 10 years earlier had lower metabolism in a key region of the frontal cortex.

Women treated with chemotherapy also showed a spike in blood flow to the frontal cortex and cerebellum while performing memory tests, indicating a rapid jump in activity level, the researchers said in a statement about their study.

‘The same area of the frontal lobe that showed lower resting metabolism displayed a substantial leap in activity when the patients were performing the memory exercise,' said Daniel Silverman, the UCLA associate professor who led the study.

‘In effect, these women's brains were working harder than the control subjects' to recall the same information,' he said in a statement."

The study appears to be of a relatively small group, whom researchers asked to perform simple memory tests while undergoing PET scans. Published in the online edition of Breast Cancer Research and Treatment, it focused on just "21 women who had surgery to remove breast tumors, 16 of whom had received chemotherapy and five who had not." The article doesn't mention whether researchers were focusing on certain chemotherapy medicines only, or whether they were generalizing to consider all chemotherapy.

Still, their findings are suggestive – although I imagine that further studies, with much larger numbers of subjects, will be needed to satisfy all skeptics.

For now, the present state of affairs will probably continue, with many doctors expressing doubts, while a significant number of patients provide anecdotal evidence that – from their point of view, anyway – chemo brain is real.

As for me, I can't say for certain that I've experienced it. Sure, in the days following each chemo treatment, I found it hard to read for any length of time, or to concentrate on complicated tasks. But I could simply attribute that to the fact that I was feeling lousy. I could have said much the same thing about times in the pasts when I've had the flu.

As for any long-term effects of chemotherapy on memory, I can't say I've noticed any of those, either. Sure, I find it hard to recall someone's name, on occasion – and there have been times when I've wondered whether that's a result of chemo brain – but I can't say for sure that's the cause. I'm going to turn 50 in a couple of weeks. You can't expect to get that far in life without the mental machinery casting off a few nuts and bolts.

Those of us dealing with cancer need to pay close attention to confirmed medical findings from research studies, but it also pays to listen to the anecdotal experience of others. That two-pronged approach to information-gathering is, I think, the best way.

October 7, 2006 - Rituxan Research Marches On

I've recently learned that Rituxan – the miracle drug that likely played a large role in the successful treatment of my cancer – has just been approved by the FDA for even wider use.

If I'm reading the Genentech company's press release correctly, Rituxan is now approved for use with another combination of chemo drugs other than CHOP: a drug cocktail known as CVP (cyclophosphamide, vincristine and prednisolone). This is for patients with follicular non-Hodgkin lymphoma – the indolent (or slow-growing) form of the disease. Rituxan is also now approved for follicular lymphoma patients whose disease is "stable," as well as for those relapsed patients who have already had treatment with CVP.

This news probably doesn't apply to me, personally, because my "diffuse mixed large and small cell" grading is considered to be an aggressive form of NHL (which means I'm already approved for treatment with Rituxan). But, I'm glad to know this medicine is now available more widely, to make a difference in the lives of others.

This is a typical illustration of how new drugs come to be available. When pharmaceutical researchers come up with a new formula that's likely to help patients, and have completed all the laboratory tests at their disposal, they must then engage in a lengthy process of testing on human subjects, a process known as "clinical trials." Clinical trials are typically divided into several phases.

Phase one involves a handful of patients, who are monitored closely to make sure the new medicine is safe to give to humans. When it comes to cancer drugs, "safe" is a relative term. Many widely-used cancer treatments have harmful side effects. Ironically, some chemotherapy agents (including some of the ones I've received) are known carcinogens. This means the medicines themselves will cause cancer in a small percentage of people who receive them. Yet, this is an acceptable risk, because avoiding the drugs is statistically more likely to harm patients. (If, for example, a drug is 80% likely to put a lymphoma patient into remission, but will cause leukemia, down the road, in an unfortunate 3% of the people who receive it, those are pretty good odds.)

Fortunately, Rituxan – unlike many of the old-line chemotherapy drugs – has only minimal side-effects.

If there are no significant ill effects in the first phase, the trial moves on to phase two, in which a somewhat larger group of patients receives the drug. Researchers monitor this group not just with regard to safety, but also in order to test the medicine's effectiveness. Often, there must be a control group, randomly selected from among the pool of clinical-trial participants. Because it would not be ethical to give sick people only a placebo (a harmless substance, of no medical value), the patients chosen for the control group typically receive another, fully-approved cancer medicine instead. Clinical trial participants don't usually know whether they are in the study group or the control group. Patients who volunteer for such studies know they may have as much as a 50% chance of not receiving the promising new medicine, but they're generally willing to take that risk – because a 50% chance of getting it through a clinical-trial study is better than the 0% chance they would have of receiving it, had they stayed out of the clinical trial.

If phase two is successful, the researchers move on to phase three, in which the new product is tested on thousands of volunteers. If the medicine proves to be both safe and effective for a significant portion of this group, then it finally receives government approval for general use.

Research continues, then, through phase four: follow-up studies that examine the long-term risks and benefits of the drug.

Clinical trials are the cutting edge of cancer treatment. That's the reason many patients – particularly relapsed patients, who are running out of other options – sometimes travel great distances to be part of them. They're especially appealing to the uninsured and the underinsured, because drug companies typically make the medicines available to test subjects for free. Typically, clinical trials – especially phase three trials – are simultaneously offered in a number of leading treatment centers around the country, and even around the world. The theory is that this puts the new medicines within reach of as large a number of patients as possible.

It's quite a process – and very costly for the pharmaceutical companies to go through. That's the reason each of my six Rituxan doses had a list price of $7,000 (although the price was somewhat reduced for me – as it is for most patients – through contractual agreements between my medical insurance company and the doctor). Thankfully, my medical insurance covered most of it.

Pharmaceutical research is big business, no doubt about it: but it's a business that, when everything is said and done, saves lives.