Part 1. "Rave Reviews" for Radiation in Treating Skin Disorders
The lucky readers who have not had skin disorders may tend to dismiss them as trivial, because they are rarely fatal. If there are such readers, we urge them to look at photographs in any dermatology text, in order to appreciate how severe and disabling skin disorders can be. Photographs, however, can not convey either pain or intense itching (pruritus), and these invisible aspects of many skin disorders are very serious ones, too.
From 1900 out to 1955-1960 at least, dermatologists made extensive use of radium and x-rays in the treatment of skin disorders. By itself, dermatologic practice may account for radiation doses of real consequence for female breasts. It is very difficult, however, to find studies which provide sufficient information for quantitative analysis (see Part 3). Thus, there is no entry at all in our Master Table for this source of breast-exposure.
We emphatically warn readers against assuming that the absence, in our Master Table, of any dose-estimate is a suggestion that the average annual breast-dose for females was negligible. On the contrary, it is possible that dermatologic radiation exposure of breast-tissue was greater than the combined sources of breast-dose evaluated in the Master Table. The fact that we have counted no dose at all from dermatologic irradiation is another source of underestimation in our finding.
Dermatologists never deny their extensive use of what they call "superficial x-ray therapy" --- which differs from therapy with the very low-energy radiation known as "grenz rays," also extensively used by many dermatologists (see Part 3). In 1922, Dr. George MacKee, one of the great figures of dermatology, published a paper with Dr. George C. Andrews, from which we quote:
"It is now pretty generally admitted that the roentgen rays constitute the most useful and successful single remedy we possess for the treatment of dermatological diseases. The only competitor for this distinguished position is radium. In a general way, what one agent will accomplish, so will the other." And:
"That the roentgen rays constitute the most valuable remedy in dermatotherapy, or that the roentgen rays and radium constitute the most useful single agents in the armamentarium of pure dermatology, is shown by the following list of diseases and conditions that are amenable to such treatment, over 80 in number." There is a small number of superficial malignancies in the list of 80, but by and large, this is a very long list of benign dermatoses which were being treated with ionizing radiation therapy. Dr. MacKee describes one use which is abundantly confirmed by scanning the literature of the times. Dr. MacKee:
"That the roentgen rays and radium are excellent antipruritics has long been known. In cases of persistent, localized, essential pruritus of undiscoverable etiology they are the only remedies that will with a reasonable degree of certainty effect complete relief [of the itching]. The relief may endure for a month, for several months, or for longer periods. Permanent results are uncommon. Occasional failures are noted."
One gets a good feeling of real integrity in reading the works of Dr. MacKee --- not only in this paper, but also in his classic text, discussed in Parts 2 and 4 below.Part 2. A Candid Appraisal in 1938 of Actual Benefits
In 1938, Dr. George MacKee published the Third Edition of his book, X-Rays and Radium in the Treatment of Diseases of the Skin. (The First Edition had been published nearly 20 years earlier.) Dr. MacKee's reputation in dermatology worldwide was one of the best in his time.
His 1938 book, published in the middle of the 1920-1960 period of our current interest, is especially illuminating --- and full of sound and sensible comments about medicine, dermatology, and what therapy is possible with ionizing radiation. Below, we quote some passages from his Preface to the 3rd Edition. Having noted that the dermatologist must know a lot about internal medicine as well as external medicine, Dr. MacKee continues (p.5):
"The foregoing paragraph is a preamble for the statement that x-rays are now employed less frequently in dermatology; and it is possible that they will be used still less frequently in the future. Dermatologists whose training has been inadequate are likely to use x-rays indiscriminately. On the whole, however, there is an increasing disposition on the part of dermatologists to employ x-rays only when necessary or when definitely indicated; in other words, with discriminating judgment. This trend is most noticeable among the older dermatologists and is the result of accumulated experience; also among well-trained young dermatologists who are capable of guidance." And (p.5):
"Thirty years ago certain dermatoses were treated with x-rays because there was no other equally efficacious remedy. Since then other methods of treatment have proved equal to or superior to x-rays in these particular affections ..." (An affection is an ailment, a disease). And (p.5):
"For a number of years, long ago, the author did not fail to cure a case of lichen planus with roentgen rays [lichen planus is a skin disorder described in our Chapter 34]; therefore, they were supposed to be almost a specific; at least they were considered the method of election. Now it is known that x-rays frequently fail to cure and in some instances they do not even modify the course of the affection. Today we know that many cases of acne vulgaris, eczema, and many other dermatoses respond better to conventional dermatological investigation and therapy than they do to roentgen therapy alone ..."
Nonetheless, Dr. MacKee still considers x-ray therapy efficacious for many skin disorders, as indicated in our Chapter 34. As in 1922 (above), he says in 1938 (p.6): "It is the consensus of opinion that x-rays constitute the most important single therapeutic agent in the armamentarium of the dermatologist." MacKee does not disassociate himself from the consensus. He continues (p.6):
"Considerable attention has been devoted [in this book] to the historical aspect. This is deemed advisable because modern skill could not exist without the efforts of predecessors in the same field of endeavor. The young roentgenologist of today knows little of the difficulties, technical and professional, encountered and overcome by the older roentgenologists; nor does he appreciate how much is owed to the roentgenologists of the past, many of whom lost their lives in an endeavor to advance the science and art of roentgenology. These men possessed the pioneer spirit to succeed and the spirit of service. Their work is an inspiration; their names should not be forgotten." And he adds (p.7):
"We are still in the pioneer period ... In the therapeutic field we are badly in need of scientifically controlled experimentation and carefully compiled statistics. We still depend too much upon impressions and beliefs."
In a short Preface, MacKee opted to allude twice (p.5, p.7) to changing observations and to excessive reliance on "impressions and beliefs." We find him refreshingly candid. A man of great experience and accumulated wisdom, a man who has built a worldwide reputation as the "dean" of x-ray and radium therapy in dermatology, seems to be saying in effect: "We are not really getting some of the results we used to think we had. We did a lot of self-suggestion, and I'm not afraid to say so." This is our interpretation of his remarks, especially in view of possible self-deception in parts of the "enlarged thymus" story (our Chapters 6 - 11).Part 3. The Problem of Dosage, and a "Safety" Claim in 1952
There is nothing intrinsically special about the use of radio-therapy for benign skin afflictions which makes it difficult to assess irradiation of the breasts, for our Master Table. There are many sources (including MacKee) which cite typical dosages for various therapies. We cite one paper below. Nonetheless, the problem for us is two-fold:
First, we need a reasonable way to estimate what fraction of such treatments actually reached breast-tissue, and second, we need a reasonable way to estimate what fraction of female persons in the population received the various therapies per age-year and per calendar-year.
Because we do not presently have a reasonable way to solve these problems, we just exclude the entire topic of dermatology from the Master Table of this edition. However, for interested readers, the next chapter surveys the skin afflictions for which radio-therapy sometimes caused irradiation of the breasts, and some which always did, including x-ray therapy for eczema of the nipple and breast, and for intertrigo under pendulous breasts.
The Development of "Grenz Rays"
There is one aspect of dermatology which undoubtedly prevented the breast-cancer price from being as severe as it would otherwise have been. In 1925, Dr. Gustav Bucky began to emphasize his ideas concerning "infra-roentgen" or "grenz rays." These are low-energy radiations of the region between ultraviolet and roentgen-rays, with a wavelength of 1.5 to 2.0 Angstroms (Bucky 1927, p.645). They have low penetration power. All their energy is absorbed within about two millimeters of tissue, which means that they do not penetrate beneath the skin.
These radiations, also called "super-soft roentgen rays," have an average energy of only 6 to 10 kilo-electron-volts or Kev (Eller 1927, p.437). It is important to know these energies, in order to know the important distinction between "super-soft roentgen rays" ("grenz rays") versus "superficial roentgen rays." In terms of penetrating power (and irradiation of breast-tissue), there is a world of difference.
Why do we accept Eller's energy-values as reliable? For a very good reason: The laws of physics. Visible light, ultraviolet light, x-rays, and gamma rays are all composed of photons, which are packets of electro-magnetic energy traveling at the speed of light. The relationship between the energy of photons and wavelength is the following (from Gofman 1981, p.12): Photon energy in kilo-electron-volts (KeV) = (12.398 KeV-Angstroms) divided by (wavelength in Angstroms). If we use 1.5 Angstroms as the wavelength of "grenz rays," the formula yields 8.3 KeV as the photon energy. If we use 2.0 Angstroms as the wavelength, the formula yields 6.2 KeV as the photon energy. So Eller's values are in harmony with the laws of physics.
The use of "grenz rays" in some aspects of dermatologic therapy became popular and widespread. There is no doubt that their use surely protected breast-tissue, whenever higher-energy x-rays would otherwise have been used for therapies involving the breast.
However, according to the source below, it was not customary to use "grenz rays" in the treatment of most skin disorders.
A Safety Claim about Entrance Doses up to 1,400 Roentgens
Early suggestions, that the use of x-ray therapy by dermatologists might be harmful, brought an emphatic denial in 1952 from Marion Sulzberger, head of the Department of Dermatology at New York University. First we will cite his statement about safety and benefits, and then we will show that his reference to treatment by "superficial" x-rays (up to 1,400 roentgens) does not mean treatment by "grenz rays." Dr. Sulzberger states (1952, p.639):
"After more than 30 years of experience, the large majority of qualified skin specialists in the United States feel certain that the use of superficial roentgen-ray treatments in the described fractional doses and within the stated limits of maximum dosage is not merely safe and justifiable but is, as a matter of fact, among the best therapeutic measures in selected cases of many benign dermatoses. For it is the recorded dermatologic experience that such treatments `cure' or materially benefit many patients with skin eruptions which fail to respond to other accepted forms of treatment, thus lessening the periods of disability and often also the risks of permanent physical or psychological damage that would otherwise result from the dermatosis."
We would have no quarrel whatsoever with Dr. Sulzberger's claim of benefit from such use of x-rays. But his claim that such treatments were safe (risk-free) is mistaken in a very big way.
How do we know that his reference to "superficial roentgen-ray treatments" could not mean "grenz rays"? We compare the kilovoltage (below) with the kilovoltage for "grenz rays" (above). Dr. Sulzberger points out carefully what qualified dermatologists did in "customary practice" for "most dermatoses" (p.639):
"In most dermatoses, the customary practice is to administer to any one area no more than 85 R weekly or 42.5 R once to twice weekly, up to a maximum total dose of about 1,400 R. These figures are based on dosages measured in air. The usual quality of irradiation used ranges from 60 to 100 kv [kilovolts], with half-value layers of about 0.5 to 1 mm aluminum; only in exceptional cases will the voltage used go as high as 120 kv, with half-value layers up to 3 mm aluminum. ["Half-value layer" describes the quality of a beam; an x-ray beam with a half-value layer of 3 mm Al is a beam whose average energy is such that a sheet of aluminum 3 millimeters thick would cut the beam's intensity in half.] For many years this quality and dosage of low-voltage roentgen-ray treatment have been used by dermatologists in the therapy of a great variety of entirely nonmalignant, non dangerous, benign skin conditions --- among them acne vulgaris, `eczema,' psoriasis, `neurodermatitis,' and severe and `intractable' itching of diverse areas."
o - ABSORBED BREAST-DOSES per ROENTGEN of ENTRANCE-DOSE. For x-rays of 0.5 mm Al., For x-rays of 1.0 mm Al., half-value layer. half-value layer. Breast Thickness: Breast Thickness: 4 cm 6 cm 8 cm 4 cm 6 cm 8 cm Absorbed Breast Rads per One Roentgen of Entrance Dose 0.284 0.204 0.161 0.406 0.315 0.250 Absorbed Breast Rads per 85 Roentgens of Entrance Dose 24 17 14 34 27 21 Ch 33, Part 3: Details in text.
Magnitude of Individual Doses to Breast-Tissue
Our focus is on the risk of radiation-induced breast-cancer, so we shall limit our comment to the breast dosage when such treatments involved the breast. The nearby box shows the absorbed dose per roentgen of entrance dose for breasts of various thickness (measured under mammographic compression) and for half-value layers of 0.5 and 1.0 mm Al. We derived the values from the work of Hammerstein (1979, especially Figures 4 and 5), for an x-ray tube having a tungsten target. These doses, plus somewhat lower doses from x-ray tubes having a molybdenum target, are from Gofman and O'Connor 1985 (Table 5, p.220).
Either set of values, or values in the same "ballpark," suffice to make our point: The beams described by Sulzberger as customary are not stopped by the skin, and they are irradiating breast-tissue at serious levels:
The lowest value in the box's second row is 14 rads of breast-dose from a single treatment. Moreover, according to Sulzberger, treatments were repeated weekly, "up to a maximum [entrance] dose of about 1,400 R." If we use the lowest entry in the box's upper row, that would mean approximately: (0.161 rad / R) x (1,400 R) = 225 rads of absorbed breast-dose for mature breasts. For female children, with all the breast-cells still close to the skin, the breast-dose per roentgen of entrance dose would be even higher.
It may well be, as noted at the outset of this chapter, that dermatologic practice accounts for more breast-irradiation than everything evaluated in our Master Table. The fact that we have no contribution from dermatology in that table is most definitely a source of underestimation in the table's sum of radiation-induced breast-cancers per year.Part 4. Comments of an "Insider" about the Years 1895 to 1938
The study of the x-ray, and what it might and might not do in medicine, has now endured through about a century of human experience. In 1938, Dr. MacKee looked back on the early decades, with the eyes of an insider, and what he tells us and what he warns us against are still relevant --- over 50 years later.
In Chapter 1 of MacKee's 3rd edition (at pages 15-16), we find frank and open criticism of those who used radiation technology in an overtly irresponsible manner. He calls them "radiomaniacs" --- a memorable term for which the context is provided below. In 1938, Dr. MacKee sees three phases in the years since the 1895 discovery:
"The history of roentgen therapy can be divided roughly into three eras --- optimistic, pessimistic and realistic; this is particularly true of this country [USA]. At first enthusiasm and carelessness overcame caution. Many physicians installed apparatus and attempted to employ the x-rays for practical therapeutic purposes, without making a study of the subject. Even the scientific and conscientious workers did not at first realize that they were dealing with an exceedingly dangerous agent. It was natural, therefore, that many patients received serious injuries." And:
"Not only were patients injured, but operators, by repeatedly testing the penetrating power of the rays by inserting their hands between the tube and a fluorescing screen, developed an erythema [a morbid redness of the skin] which in many instances led to serious sequelae. These facts, together with the discovery by Brown and Osgood that sterility was produced by the x-rays naturally caused the operators to be a little more cautious. However, optimism reigned until about 1906." And:
"During those years the rays, to a large extent, were empirically used and they were tried out on nearly every chronic disease. The literature was misleading, as it was full of case reports of wonderful cures, the occasional paper from the pen of a good man being ignored or overlooked by the average x-ray operator of the period and in spite of repeated warnings from capable men, the `radiomaniacs' held the reins."
The Pessimistic Period
Dr. MacKee goes on to describe the disappointments which came with the realization that cancer was not to be conquered by x-rays and that the "x-rays proved practically useless in pulmonary tuberculosis. This was another great disappointment" (p.16). After describing some "very curious theories" concocted during the period, MacKee comments (p.16):
"In fact, the literature contained many erroneous and even dangerous theories. The unverified accounts of marvelous results, the injurious effects observed as time went on, the fact that there was no satisfactory method of estimating the amount of radiation administered, and the fact that the earlier claims were not substantiated, finally resulted in the period of depression or pessimism which lasted from about 1906 to about 1910 or 1912." And:
"During this period there were a number of scientifically inclined roentgenologists who recognized both the advantages and limitations of the x-rays and who also recognized the necessity of standardizing the work and of devising accurate methods of measurement."
The Realistic Period
At the end of Chapter 1, Dr. MacKee is describing his contemporary period of roentgenology, which was "realistic" in his view. He closes the chapter with two paragraphs (at page 18) whose optimism is worth pondering:
"In addition to the accomplishments of scientifically inclined physicians and electrical engineers, it must not be forgotten that many physicists, biologists, chemists, and physiologists persistently investigated the x-rays and radioactive substances from the very moment of their discovery. The work of these men paved the way for most of the improvements in the technic of recent years and, of course, as a result of their tireless endeavors we now possess a fairly reliable conception of the nature of the x-rays and of the radioactive substances." And the final paragraph:
"At last the value and limitations of the x-rays in the treatment of disease have been fairly well established; especially is this so of cutaneous affections. The improvement in technic, increased knowledge regarding possibilities and limitations, the recognition that roentgenology is a specialized subject, and especially the fact that radiodermatitis can be avoided with a reasonable degree of certainty, have caused a gradual restoration of confidence and this confidence will be permanent if the work can be kept out of the hands of unscrupulous, overenthusiastic and careless individuals."
"If," says MacKee. He alludes to an eternal and universal human problem, occurring in not just one occupation or society.Part 5. The Relevance Today of Dr. MacKee's Lessons
Dr. MacKee would surely be horrified, we think, to learn the sad consequences from excessive radiation administered during the subsequent decades, even in the hands of the best-intentioned physicians and scientists. New technologies having a biological impact can be introduced only at some low rate, or else the price can be tremendous in life and health before the cause is recognized. We believe Dr. George MacKee would very probably be in the forefront of those agreeing with such an opinion today.
1942: An Enthusiast for More Use of Medical Radiation
In 1938, Dr. MacKee held the opinion that "We are still in the pioneer period" of radiation therapy (1938, p.7). The spirit of the times is clear also in the famous text, Christopher's Surgery.
In 1942, its Third Edition provided Chapter 36 entitled "Roentgenology: Diagnostic and Therapeutic Roentgenology in Surgery." The author of the chapter was Dr. James Thomas Case, Professor of Radiology at Northwestern University Medical School. After listing some radiation therapies of probable interest to surgeons, Dr. Case explicitly tries to inspire expanded use and exploration "of this rapidly developing method of attacking certain diseases" (Case 1942, p.1636):
"Many lesions of a benign character respond to radiation therapy, such as tuberculous glands of the neck, abdominal tuberculosis and some cases of joint tuberculosis, interstitial fibroid tumors when not larger than a three or four months' pregnancy and metropathic hemorrhages. Toxic adenomas [a type of tumor, usually benign] when not too large usually respond well, but the treatments must be continued over a period of three to five months, all the doses being suberythema [below the dose which causes morbid reddening of the skin --- about 300 R] and with adequate filtration. Furuncles, carbuncles, cellulitis and erysipelas respond promptly to minimal doses. Recently the employment of x-ray in small doses in the therapy of gas gangrene has appeared very promising. Buerger's disease and Raynaud's disease respond nicely to roentgen therapy over the lumbar sympathetic system, often averting the need for amputation. The only worthwhile treatment for leukemia is roentgen therapy, which is also useful in erythremia, Hodgkin's disease and lymphoblastomas of any type." And then:
"No attempt has been made in the foregoing to cover adequately the field of roentgen therapy, but rather to arouse the physician's natural investigative instinct to look at more length into the possibilities of this rapidly developing method of attacking certain diseases."
People Will Learn, One Way or the Other
Some medical uses of radiation were and are enormously helpful to patients. But not all of the uses. In 1938, Dr. MacKee was warning his colleagues against self-deception and carelessness with respect to certain uses of radiation. We have little doubt that many physicians who caused breast irradiation in the course of their roentgenologic work would prefer --- with the benefit of hindsight --- to have used much lower doses or not to have done it at all. We know some of them personally.
From the point of view of a student, not a critic, we wish to comment on the importance of learning from the Dr. MacKees and from past experience in general, in order to avoid tragedies in the future. It would be appalling if medicine were unwilling to accept, or to make, an honest evaluation of the cancers induced by medical irradiation.
There are some reasons for optimism. For example, certain practices with x-rays are long out of use, in dermatology and other aspects of medicine. On the other hand, some other uses are increasing. It will require real vigilance with respect to radiation technologies and their uses, in order to insure that the lessons of the past ten decades succeed in preventing an equal amount of cancer-causation in the future. And the vigilance needs to come from an educated populace, especially women.
People will learn, one way or the other, that they themselves are the ones most likely, by far, to have an intense and enduring concern for the health and well-being of themselves and their own family.
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