RADIATION ADVOCATED AFTER SURGERY FOR DCIS

In an article appearing in the current issue of the Lancet (July 12, 2003), scientists report that radiation therapy after surgery can reduce the risk of breast cancer recurrences in women with ductal carcinoma in situ (DCIS). DCIS is a precancer that occurs when the cells that line the milk ducts in the breast show cancer-like changes. It is not exactly cancer - more like a risk factor for the disease. The proper treatment of this increasingly common condition is controversial.

When DCIS is limited in scope, it may be treated by removing the affected part of the breast ('lumpectomy'). But what then? Radiation and the anti-estrogenic drug tamoxifen may be prescribed. If DCIS is extensive, then a full mastectomy may be suggested. But not all doctors are convinced that such aggressive treatments are really necessary.

A recent clinical trial reported in the Lancet tested several post-surgery options in over 1,000 women in Britain, Australia and New Zealand. All of these women first had excisional surgery and then received either radiation therapy or tamoxifen, or both. The results showed that radiation reduced the risk of a recurrence of DCIS in the same breast by 60 percent and the risk of invasive cancer (i.e., cancer which has spread beyond the ducts) by more than 50 percent. Statistics such as this can give a false impression of the value of the treatment. Actually, the chance of having a recurrence in the affected breast decreased from 5.3 percent in the control group to 2.5 percent in the radiotherapy group, which is an absolute risk reduction of just 2.8 percent.

Prof. Jack Cuzick, an epidemiologist with the charity Cancer Research UK, who led the study, has concluded that most women should therefore get radiation therapy for DCIS. By contrast, tamoxifen was essentially of no use for such patients. "Radiotherapy works just as well in the presence or absence of tamoxifen," Cuzick told reporters. Dr. Cuzick said that his research supported the findings of two earlier studies that also showed the benefits of radiation for DCIS patients.

DCIS accounts for about a quarter of all breast cancers that are detected by mammograms. There are three grades of the condition, low, medium and high. If left untreated, DCIS can develop into invasive cancer, but this does not by any means always happen. Not surprisingly, women who have low grade DCIS are least likely to have a recurrence. Cuzick has said that the next clinical trial will focus on the question of whether women who have a low risk of recurrence might benefit from radiation therapy.

What Radiation Does Well

It should come as no surprise that radiation therapy helps to prevent the recurrence of DCIS and breast cancer. That is what radiation does well for many forms of cancer. The key questions that puzzle many observers are these: (1) Does radiation therapy actually increase overall survival and/or enhance quality of life for those who take it? (2) What are the long-term costs - physical, emotional and financial - of this treatment?

Nothing is said in the Cuzick study about the impact of radiation on survival. The paper simply states that just 45 (out of 1,030) patients died during the follow-up period. For 23 of these patients, the cause of death was breast cancer - or at least, breast cancer was present at the time of death. Of the remaining 22 deaths, nine were attributed to cancers other than breast, four to cardiac failure, two to vascular events, and two to other causes. Data were missing for five patients. It is not specified which of these deaths occurred in the various treatment groups. "There are too few deaths for a meaningful analysis of cause of death by treatment," said the authors. In any case, the risk of dying of breast cancer after surgical excision of DCIS is small. And one cannot say that radiation has any impact at all on survival in this population.

As to the cost of radiation therapy, the paper also says nothing, and it is difficult to find reliable data. But a 1997 Canadian study showed that the cost of giving adjunctive radiation for breast cancer was around $7,000 per patient (Dunscombe 2000). I don't know what that would equal in today's US dollars, but if we postulate that medical inflation since then cancels out the depreciation of the Canadian dollar, that yields the basis for a reasonable guess. Since the American Cancer Society estimates that there will be 47,345 US cases of DCIS in 2003 (ACS 2003), this works out to more than $331 million per year, just for the radiation portion of the treatment. In an era of cost cutting, this must be factored into the equation.

This well-documented study shows that radiation, when added to limited surgery, greatly decreases the number of recurrences of breast cancer following treatment for DCIS. But many of these recurrences could be dealt with by further surgery, when and if they occur. The study does not show that radiation actually improves survival from this pre-cancerous condition. Nor does it show that tamoxifen is of any benefit, either alone or combined with radiation, in treating this stage of the disease.

I worry about the long-term health effects of radiation therapy. We know, for instance, that in earlier studies of breast cancer, unexpected long-term damage to the cardiovascular and immune systems vitiated any immediately beneficial impact of radiation. Radiation is also a "perfect carcinogen," which can both initiate and promote tumor formation. For that reason, I would not be so quick to make adjunctive radiation part of the standard protocol for this precancerous condition.

IN MEMORY OF ROBERT A. GOOD

"He was a man, take him for all in all, I shall not look upon his like again." --Shakespeare, Hamlet, Act I, Scene ii

Dr. Robert A. Good, MD, PhD, a celebrated cancer researcher, died on June 13, 2003 at the age of 81, after a long battle with esophageal cancer. Dr. Good was Physician-in-Chief of All Children's Hospital in St. Petersburg, Fla., Director of the Children's Research Institute and Distinguished Research Professor at the University of South Florida. He was considered by many to be the father of modern immunology.

The last time I saw or spoke to Dr. Good was in 1977, when I was a science writer (and assistant director of public affairs) in his employ at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City. My memories of him are of an extremely vigorous man, then at the height of his powers and influence. He was always a bit unconventional in his dress and manner. Nowadays on the Internet, one sees pictures of him in shirt and tie, but back in his Sloan-Kettering days he cut a dashing figure with his turtleneck, sneakers and outsized peace symbol.

In 1973, Dr. Good had been appointed director of Sloan-Kettering Institute, and his face was soon familiar to many from the cover story that Time magazine ran on him.

To view Dr. Good on the cover of Time (March 19, 1973) please click or go here:
http://www.library.georgetown.edu/dept/speccoll/time/images/jpg/16.jpg

In a field filled with intensely ambitious people, Bob Good stood out for his exceptional drive, intelligence and charisma. He was a pediatrician, pathologist and microbiologist who received a combined MD-PhD from the University of Minnesota at the age of 25, an extraordinary start to an extraordinary career. He was the first person to perform a human bone marrow transplant, effectively creating a new branch of medicine. He was also the first to clearly differentiate between human T and B lymphocytes, and among many other things, he elucidated the importance of the thymus gland and rescued the lowly tonsil from medical scorn, demonstrating that these organs were important components of the immune system. This reversed a 50-year trend of needlessly destroying them through radiation and surgery.

Dr. Good was a prolific author, writing or co-authoring over 2,000 articles and 50 books, certainly something of a record. He was also a great pioneer in the field of nutrition and cancer. Readers of this newsletter may recognize his name from the foreword he wrote to Charles B. Simone's book Cancer and Nutrition. With Gabriel Fernandes and Edmund J. Yunis, in the 1970s, he began an exploration of the effect of dietary restriction on cancer incidence and survival in mice. There is no question that he deserved the Nobel Prize for Physiology or Medicine many times over. That he did not receive it had nothing to do with merit and much to do with the scandals that marred his years at Sloan-Kettering.

It was my exceptional good fortune to begin my career as a science writer under the tutelage of this brilliant and eccentric mentor. It was from him that I first learned how a great scientific mind works. He hired me in the spring of 1974, when his own tenure at Sloan-Kettering and the entire "war on cancer" were brand new. During the process of applying for this job I had to submit to interviews with all the leaders of Memorial Sloan-Kettering Cancer Center (MSKCC). I well remember meeting with Lewis Thomas, MD, president of MSKCC, who stared at me vacantly through a cloud of pipe smoke, as remote as the hookah-smoking caterpillar in Alice in Wonderland. Perhaps he was thinking about his next essay for the New England Journal of Medicine, soon to be published as the award-winning book, Lives of a Cell. Whatever the reason for his remoteness, my interview with him (and every subsequent encounter) was both mystifying and intimidating.

How different was my first encounter with Dr. Good, who was filled with enthusiasm for the work being done at Sloan-Kettering. He had a need to explain, convince and inspire. Something in his tone of voice told you that a cure for cancer was possible, perhaps even imminent! We talked about everything from the origins of cancer to the differences between research in the sciences and the humanities. I well remember him telling me about Vilhjalmur Stefansson, the famous Arctic explorer, who claimed that cancer was "a disease of civilization". Dr Good also spoke about the exciting work on cancer immunology which he was then performing along with his co-workers Drs. Lloyd Old and Edward Boyse. (My colleagues and I later dubbed these three great immunologists the "Good Old Boyse").

After I was hired, I wrote so many articles in MSKCC's Center News about him and his protégés that some scientists complained that the new director was monopolizing my services. Or, conversely, they accused me of playing office politics. But as I surveyed the entire work of Memorial Sloan-Kettering, an institution of 4,600 employees, I found myself gravitating over and over again to the work of Dr. Good and his colleagues. Not for nothing had they made him the Director.

Dr. Good was as unconventional in his work habits as he was in his dress. His day began well before sunrise, and friends, colleagues and employees were expected to accommodate themselves to this grueling schedule. He also thought nothing of keeping people waiting hours to see him. I took this personally until the day I saw James Watson, PhD, co-discoverer of DNA, cooling his heels in Good's outer office! In time, despite huge differences in our professional standing, Dr. Good and I became close. On occasion, I would travel the subway in the predawn darkness to attend an early morning meeting in his office.

The high point in our relationship came in 1977, when (by a strange concatenation of events) Dr. Good and I dined together at New York's famous 21 Club. We were planning to write a book about his travels in China, then still a novelty. In the course of the dinner, however, he said something privately to me that certainly gave me pause. "You and I are not so different. We are both employees. You can be fired, and so can I," he told me in a fatherly way. In the light of what was to come, these words were little short of prophetic.

Not long after taking up his post at Sloan-Kettering, Dr Good became embroiled in the Summerlin Affair, a scientific scandal that, unfortunately, remains indelibly linked to his name. Dr Good hired and sponsored a young researcher named William Summerlin, MD, who claimed to be able to transplant tissue between genetically unrelated animals, a feat which, if valid, would have been one of the greatest breakthroughs in medicine. To prove the validity of his astonishing claims, Summerlin demonstrated white mice with black patches on their backs allegedly transplanted from unrelated donor mice. However, after Summerlin made one such "dog and pony show" in Good's office, an astute technician noticed that the black patches on some of the mice had inexplicably changed. The technician found that these 'transplanted patches' were actually drawn on the skin of the mice with a felt-tipped marker, and he was able to remove the patches with alcohol. This discovery led to one of the most sensational scientific scandals of the 20th century.

I myself arrived at Sloan-Kettering in the spring of 1974, just as the Summerlin story was breaking. Many people, including some inside the institution, thought that Dr. Good himself was personally culpable in the deception. He was, they pointed out, senior author on Summerlin's papers. However, an official MSKCC panel concluded that he was not directly responsible, although it did reprimand him for not properly supervising his young colleagues. Summerlin in turn blamed the "pressure cooker" atmosphere within Sloan-Kettering for his transgressions. His reference to a "pressure cooker" was widely seen to be an allusion to the results-oriented atmosphere generated by Dr. Good.

With the hindsight of nearly 30 years, I sympathize with Dr. Good. I can well understand how he was betrayed by his own enthusiasm. In essence, he was a trusting man in a field that depends, in great measure, on one's ability to rely on the honesty of one's colleagues. What Summerlin proposed was startling, to be sure, and more prosaic minds rejected it simply for that reason. But Dr. Good understood that any major discovery was, by its very nature, bound to be surprising. He was also taken with the beauty of Summerlin's idea. Perhaps his enthusiastic imagination, and his intense desire to find cures (and, naturally, to have them connected to his name) got the better of his scientific objectivity. I don't think that either he, or any of the other leaders at Sloan-Kettering, seriously considered the possibility that Summerlin's research might be a hoax. Even today, it is something one almost never thinks of in regard to colleagues - which is precisely why sociopathic tricksters can wreak such havoc in medicine.

There were less seemly factors at work as well. Sloan-Kettering was approaching a financial crisis, caused in part by the administration's extravagant spending on new projects. A discovery of this magnitude would have attracted all sorts of money and might have rescued the institution. Good himself deserved to win the Nobel Prize for his work on T cells and on bone marrow transplantation. It was inexplicably delayed, perhaps by enemies who called him the "Sammy Glick" of modern science (after the anti-hero of Budd Schulberg's novel, What Makes Sammy Run?) If Summerlin's research had proved valid, Good would have been internationally feted. But, essentially, I feel that he was a tragic victim. His openness and intelligent enthusiasm, while certainly the source of much of his personal charisma and power, also laid him open to the wiles of charlatans. I know it was devastating for him to learn how an unscrupulous person had taken advantage of his most appealing trait.

My own parting of the ways with MSKCC came a few years later. I have written in detail about this in my book, The Cancer Industry. The week after I was fired, the journal Science interviewed Good. He said that I knew his "innermost thoughts." But I certainly never learned his innermost thoughts on why he and his colleagues issued misleading statements on the nature of MSKCC's laetrile experiments. It was a painful and disappointing end to our relationship. And then, not long after my departure, Dr. Good was himself dismissed from Sloan-Kettering, a strange fulfillment of the prediction he made during that dinner conversation with me years earlier.

Relationship with Dr. Gonzalez

Others in alternative medicine had similarly complex and troubled relationships with Dr. Good. Nicholas J. Gonzalez, MD, was another who was befriended by this outstanding mentor. While still a student at Cornell University Medical College, Gonzalez convinced Good to supervise his research into the dietary cancer treatment proposed by William Donald Kelley, DDS. Both Good and Gonzalez thought that they would quickly expose this "fraudulent" therapy. Yet to their amazement, Gonzalez was able to document many unexpected remissions.

Although Dr. Good later minimized the importance of his relationship with Gonzalez, in fact they were very close. Gonzalez lived in Good's home for weeks at a time and followed him into his "Babylonian exile" in Oklahoma and then Florida after he left Sloan-Kettering. Dr. Good served as best man at his young protégé's wedding. But in the late 1980s, Gonzalez made the momentous decision to become a full-time practitioner of the Kelley method and to set up a private practice in Manhattan. Dr. Good was scandalized by this unequivocal embrace of alternative medicine. At that point, their relations became estranged. Not long ago, Dr. Good even appeared on national television, denying that he ever had a close and supportive relationship with Gonzalez! Now, ironically, Gonzalez is becoming not just famous but also quite respectable, with a clinical trial of his methods financed by the National Institutes of Health. Good saw the potential value of the therapy but (always, I believe, with one eye on the Nobel Priz that never materialized) shied away from even the hint of controversy.

Like all of us, Robert Good had his weak as well as his strong side. However, as serious as were his flaws, he had a tremendous and beneficial impact on almost everyone he came in contact with, including thousands of patients, colleagues and students. He could be incredibly inspiring to young people. Despite how our relationship ended, I am proud to number myself among those who were taught, nurtured and befriended by this outstanding individual.

--Ralph W. Moss, Ph.D.

References:

American Cancer Society, Cancer Facts & Figures 2003. Available online at:
http://www.cancer.org/docroot/STT/stt_0.asp

Barclay, Laurie. Radiotherapy Helpful After Excision of Ductal Carcinoma in Situ. 7/10/03. At:
http://www.medscape.com/viewarticle/458505

Dunscombe P, et al. A cost-outcome analysis of adjuvant postmastectomy locoregional radiotherapy in premenopausal node-positive breast cancer patients. Int J Radiat Oncol Biol Phys. 2000;48:977-82.

Fernandes G, Yunis EJ, Good RA. Influence of diet on survival of mice. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1279-83.

Summerlin WT, Broutbar C, Foanes RB, Payne R, Stutman O, Hayflick L, Good RA. Acceptance of phenotypically differing cultured skin in man and mice. Transplant Proc. 1973 Mar;5(1):707-10.

Saxon, Wolfgang. Robert A. Good, founder of modern immunology, dies. New York Times, June 18, 2003. Available at:
http://www.nytimes.com/2003/06/18/obituaries/18GOOD.html?ex=1058414400&en=7715ca2087a844e7&ei=5070

UK Coordinating Committee on Cancer Research (UKCCCR) Ductal Carcinoma in situ (DCIS) Working Party on behalf of DCIS Trialists in the UK, Australia, and New Zealand. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet 2003;362(9378):95.

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.

CancerDecisions® PO Box 1076, Lemont, PA 16851 Phone Toll Free: 800-980-1234 | Fax: 814-238-5865 Copyright © 1996-2004 All Rights Reserved