Cancer Decisions - Free Newsletter -September 20, 2003

DOES TRAVELING FOR TREATMENT INCREASE SURVIVAL?

There was a surprising study in this week's issue of the Journal of the National Cancer Institute. Researchers at Massachusetts General Hospital studied the impact that traveling for treatment had on survival, specifically the survival of 110 cancer patients who were being treated in Chicago over a 7-year period. They showed that patients who traveled to receive cancer treatment survived longer than those who were treated within 15 miles of their home.

It was previously known that patients who traveled for treatment tended to survive longer. This phenomenon had even been given a name-"referral bias" or "distance bias." One easy explanation for referral bias in general is that patients who can afford to travel are able to receive more sophisticated and effective treatment. But that explanation clearly didn't hold true in this case.

What is truly surprising about the current study is that all of the patients had the same diagnosis, took part in the same Phase II clinical trial, and received the same or comparable treatments. (They all had regionally advanced squamous cell carcinomas of the head and neck region and all received a particular combination of chemotherapy and radiation.) Yet those who came from a distance did better-in fact MUCH better-than those who happened to live near the treatment center. Those who traveled more than 15 miles for treatment astonishingly had just one-third the risk of death of those who lived closer to the treatment center! Similar results were observed for progression-free survival, another key measure of response to treatment.

Other more predictable factors that influenced survival were age, race, family income, smoking history, and tumor stage. But "after adjusting for the previously mentioned variables…the hazard of death decreased by 3.2% with each 10 miles the patients traveled for treatment," Dr. Elizabeth Lamont and her colleagues at the Massachusetts General Hospital Cancer Center, Boston, explained.

"Our study formally documents something clinical researchers in oncology have long appreciated," Dr. Lamont commented. "That is, on average, those patients who are able and willing to 1) research therapeutic options (or have agents who will do so for them) and 2) find and expend the resources necessary to then receive those therapies seem to fare better than those patients who end up at the closest place for care, even if their disease and treatments are apparently the same."

What makes this finding so provocative is that although the patients all received the same treatment, clearly they must have differed significantly in some as-yet-unidentified psychological or sociological way.

I have frequently observed this phenomenon, which (as Dr. Lamont has shown) is independent of the patients' economic status. My belief is that patients who carefully and deliberately select a treatment, and then travel to receive it, obtain a psychological lift by exercising their medical freedom of choice. They probably feel more optimistic about their disease and the possibility of cure. I believe that an indefinable "will to live" can influence survival. Perhaps that is the difficult-to-measure phenomenon that these scientists are now bumping up against.

I also believe that such self-directed patients are more likely to use adjunctive complementary and alternative measures than are the average patients. Dr. Lamont and her colleagues should question these patients on their use of antioxidants, herbs, meditation, etc. before, during and after receiving radiation and chemotherapy. The judicious use of such approaches might help explain their dramatically better survival.

People have traveled for cancer treatment for a very long time. In the 19th and early 20th century this became something of a mania. I have a century-old book that attempts to explain the impact of climate on disease and describes literally hundreds of health resorts and mineral springs in Europe alone (Cohen 1901). Germans still frequent their spas in great numbers. *See photo below.

Spa at Baden-Baden, Germany

Nowadays, there are scores of clinics, many of which are located in spa towns, that cater to international patients, including those with cancer. There are also an increasing number of similar facilities in the United States and elsewhere. Many cancer patients travel long distances to be treated at these places. I am sure that the very act of traveling to receive a new treatment has an uplifting effect on many patients. But making a good treatment decision under present circumstances is not easy. Some clinics do offer promising treatments that are not readily available in one's home territory. Yet others, sad to say, are thinly veiled rip-offs. They may even cause harm and shorten survival. Sometimes it is difficult for even experienced investigators to tell the difference between the two.

Dangers of Phase II Trials

The Lamont study also provides extremely important lessons about the evaluation of new cancer treatments, in particular the danger of allowing the Food and Drug Administration (FDA) to use Phase II trials as the basis for new drug approval. "If the studies they considered had been restricted to distant patients," wrote Duke University biostatistician Stephen L. George, in an accompanying editorial, "the overall results would have been impressively positive. Conversely, had they been restricted to local patients, the results would have been discouragingly negative."

Thus, selection bias, which is a distortion introduced during the enrollment process of clinical trials, "can seriously damage the external validity of trials." Simply put, says Dr. George, "patients enrolled in clinical trials often bear little resemblance to the larger population of patients to which we wish to generalize the results because of the complicated processes by which patients are identified and recruited for clinical trials." Yet many new cancer drugs are given accelerated approval on the basis of just such Phase II trials. And oftentimes the yardstick used to evaluate success is not whether the drug in question extends life but simply whether or not it temporarily shrinks tumors. As I showed in my book, Questioning Chemotherapy, tumor shrinkage, which oncologists call a 'response', is not a reliable predictor of improvement or overall survival.

Anyone interested in the thorny question of how the FDA has given a green light to ineffective treatments (which Dr. George calls "toxic placebos") should consult these two important articles. They are instant classics in the field of oncology.

I will be discussing this subject further in next week's newsletter.

The Moss Reports

I made my first visit to a foreign cancer clinic in 1976, when I took time off from a scientific meeting in Anaheim, California, to visit a Tijuana cancer clinic. I became convinced at that time that some important work was going on in some of these foreign clinics and that (despite incessant warnings about "false hope") most patients who sought treatment at such clinics felt positive about the overall experience. I still believe this to be true.

However, dubious establishments still flourish, and one of the purposes of the Moss Reports is to help our clients identify and avoid the useless or even dangerous places, and to assist them in focusing their choices on those practitioners and treatments that are credible and reliable. We offer written reports on several hundred separate cancer diagnoses as well as individualized research and phone consultations. Please go to our website, www.cancerdecisions.com, or call 800-980-1234 (from outside the US call 814-238-3367) for further information. We would be happy to put our several decades of experience at your service.

--Ralph W. Moss, Ph.D.

References:

Cohen SS. A System of Physiologic Therapeutics. Philadelphia: Blakiston's, 1901.

George, S. L. (2003). Selection bias, phase II trials, and the FDA accelerated approval process. J Natl Cancer Inst 95: 1351-1352

Lamont EB, Hayreh D, Pickett KE, et al. Is patient travel distance associated with survival on phase II clinical trials in oncology? J Natl Cancer Inst 2003; 95: 1370-1375. At: http://jncicancerspectrum.oupjournals.org/cgi/content/abstract/jnci;95/18/1370

Moss, Ralph W. Questioning Chemotherapy. State College: Equinox Press, 2000. To order go to: http://ralphmoss.com/html/books.shtml

Pogge RC. The toxic placebo, I: side and toxic effects reported during the administration of placebo medicine. Med Times. 1963,91:14.

Press coverage of Lamont article: http://www.medscape.com/viewarticle/461673

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IMPORTANT DISCLAIMER

The news and other items in this newsletter are intended for informational purposes only. Nothing in this newsletter is intended to be a substitute for professional medical advice.