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Radiotherapy of Benign Diseases:   Overview by Dr. Dewing

Part 1.   Additional Types of Breast-Irradiation
             Not Evaluated in the Master Table

          For anyone seriously interested in the endeavor to reconstruct annual average breast-doses during the 1920-1960 era, a welcome addition to the available sources is the 1965 book by Stephen B. Dewing, M.D.:   Radiotherapy of Benign Disease. The book addresses its topic in a most comprehensive, lucid, and fair manner, and the bibliography is excellent. In 1965, Dr. Dewing was Director of Radiology at the Hunterdon Medical Center in Flemington, New Jersey, and Associate Clinical Professor of Radiology at the New York University Post Graduate Medical School in New York City.

Dr. Dewing's Defense of Benign Radiation Therapy

          Dr. Dewing wrote the 1965 book because he had often felt frustrated that no single source provided the details of radiation therapy of benign diseases --- just when the physician wanted those details urgently. And he acknowledged some related concerns in his Introduction (p.ix):

          "I admit to a strong sympathy for the under-dog. I would like to correct what appears to be an unfair downgrading of benign therapy. The real point is that radiation therapy of benign conditions is a healthy and respectable subject in its own right." And (same page):

          "It has been said that radiation therapy has been used promiscuously, on every disease there is, and probably so. Give credit for zeal! The same can be said of any new drug. Certainly, quite a few conditions have departed from our repertoire through discovery of more effective methods, or due to poor results. But the scope of benign radiotherapy remains very extensive, and new applications continue to appear. Old ones die hard too. The therapist ought to be prepared to treat tuberculous cervical lymph nodes, carbuncles, erysipelas, or other such unusual lesions. Even if many such diseases seem rare, there will always be some patients who need radiotherapy --- either because there is no better treatment, they do not respond to simpler measures, or they are sensitive to a specific drug." And he makes a related comment in his first chapter (p.4):

          "Discussion of radiation therapy of many benign conditions seems to arouse a skeptical, or amused, or contemptuous, or even hostile attitude in many physicians unfamiliar with it. Part of this block may be expressed as a suspicion of empiric therapy generally but much more is due to natural preference for the modes of drug or surgical treatment that they know and trust --- radiation is very strange to them."

          We might find ourselves in a totally friendly disagreement with Dr. Dewing on a number of his statements --- particularly concerning the harmlessness of certain procedures --- and we think Dr. Dewing would also find himself in disagreement with some of his own statements, in the light of subsequent information. We certainly find ourselves in disagreement with some of our own past opinions as new information and insights develop.

Our Application of Dr. Dewing's Book in This Chapter

          We are trying to identify all sources of past breast-irradiation, and Dr. Dewing's book reveals many which will probably surprise readers. They occur in his section on treatment of inflammatory conditions.

          Because our interest (in this book) is limited to irradiaton of the breast, our application of Dr. Dewing's book will not convey the full scope of his work. For example, he has very interesting chapters on radiation therapy for "Disorders of Function and Overgrowth" (mostly of the uterus), and for benign disorders of the eye (presented with the collaboration of Dr. Manuel Lederman). Also, we will skip over his coverage of radiation therapy for benign skin disorders (presented with the collaboration of Dr. Ralph W. Grover), because we have already covered that topic in our Chapters 33 and 34.

          By itself, Dr. Dewing's book has clear limits for our effort, because he focused on the 1950-1965 period. Dr. Dewing was explicit about the time-period in his Introduction, at page "x":

          "No effort has been put into developing the historical aspect. Descriptions of the earliest explorations of any particular subject have been sacrificed to brevity and concentration on current technics. In regard to a number of diseases which were once regularly treated with radiation, but now are not, no time or space has been allotted to them." And:   "The material is drawn from a review of the American and major European radiologic journals since 1950. Numerous other foreign and domestic sources have been used as the occasion warranted, but material prior to 1950 has usually been cited only when intrinsically important or when little significant on the subject has appeared since."

          Despite these limitations with respect to our particular endeavor, we are very pleased to acknowledge that Dr. Dewing's excellent book taught us a great deal. We shall try to pass along a selection of information which is relevant to the task at hand.

Part 2.   The Observed Efficacy
             of Radiation Therapy for Inflammatory Disorders

          Dewing at p.22:   "The application of radiation to inflammatory conditions dates from radiology's earliest days. Partly as a result of the observed skin erythema (and epilation) from diagnostic or accidental x-ray exposure, and partly from comparison with the currently popular ultra-violet light treatment, physicians were tempted to experiment with treatment of skin diseases (both inflammatory and other) as early as the period 1896-98." And:

          "The empiric approach, with small to moderate doses, was so rewarding that the method continued to develop. Over the next 30 to 40 years it was extensively applied to a wide variety of inflammations." And:

          "Naturally, a theoretical basis for treatment was sought. It was found quite early that to kill or halt growth of bacteria required doses of many thousands of roentgens (10,000 R and up); far beyond even the range of cancer therapy. This meant that any direct effect on microbes could be ignored in a field where a few hundred roentgens were clinically effective. Besides, a direct effect on infectious organisms would have done nothing to explain favorable results in sterile non-infectious inflammations."

          "The practical fact remains that radiation does something to the inflammatory process. If applied early enough it may even abort it; later it tends to accelerate resolutions with either absorption or drainage. Pain relief is usually a prominent feature, too, roughly paralleling the reversal of inflammatory activity."

          "It is interesting that after reviewing all the theories they ended up just about where they started:  this or that may happen, but there is no real proof. Again, we are left with the empiric situation that we have a therapy that works --- works well enough, whether or not we know why, to make it useful and valuable in practice."

The Two Major Classes of Inflammatory Diseases

          Dewing at p.23:   "Inflammations can be divided conveniently into those which are caused by infection with some micro-organism, and those which are not."

          In the summaries which follow, we will use the same division.

Part 3.   Inflammatory Conditions Caused by Infections:   Radiation Therapy

          We are interested (here) only in the conditions for which radiation did cause or may have caused breast-irradiation.

          It would be hard to say too often in our book that we do not pass judgment on these therapies with radiation. They were used --- and that is our central fact. We need to know the extent to which their use irradiated female breasts, for the purpose of evaluating breast-dose and its contribution to the recent, current, and future breast-cancer problem.

o - Pyogenic (Pus-Forming) Infections

          Dewing at p.23:  "Therapy of the pyogenic infections has undergone a considerable revolution since the sulfonamides ushered in the antibiotic era in the latter 1930's. Before that the surgical principles of appropriately applied heat, soaks, drainage, and occasionally excisions, were the standard measures, plus native resistance and nursing care. With these the milder infections usually ran their course and the patient recovered. But up to the time when antibiotics entered the field radiotherapy also played a significant role in the tougher problem cases, and even in the routine ones when given a chance. It still does have a place, though a greatly reduced one, in exceptional situations."

          We continue to seek evidence from which we can someday make a calculation of dose to breast-pairs from the following infections which were once commonly treated with radiation:   Anthrax, diphtheria carriers, erysipelas, mastoiditis, pneumonia (additional to Rousseau's series, which we covered in Chapter 18), and gonococcal arthritis.

          "Some infections have been almost completely eradicated by the widespread use of chemotherapy," says Dewing. "An example is acute osteomyelitis in children, which as recently as the 1930's was far from uncommmon but nowadays is a rare disease. Radiation therapy was used quite often for it, and scattered articles describing such treatment have continued to appear, as recently as 1960."

          We would very much like to know the extent to which osteomyelitis and its therapy involved breast irradiation.

          Acute infections, such as cellulitis, furuncle, and carbuncle were commonly treated by radiotherapy, but rarely so treated by 1965, when Dewing's book was written. These particular infections, especially in the neck, the axillae, and the chest definitely could have delivered appreciable doses of radiation to the breasts.

o - The Fungus Diseases

          These are already covered in our Chapter 34.

o - Tuberculosis of the Lymph Glands (Not the Lung)

          We have dealt with certain aspects of pulmonary tuberculosis in earlier chapters, and we have calculated annual average breast-doses from some of the collapse therapies (Chapter 15). Here we wish to deal with a totally different aspect of tuberculosis infection, namely tuberculosis of the lymph glands.

          We think Dewing has stated the situation well, and we quote him directly (p.38):

          "Tuberculous lesions of practically every organ and every type have been treated with x-ray, with at least fair to good results. Most of these are of purely historical interest now, though therapy of peritonitis and salpingitis lingered on into the early years of the antibiotic and chemotherapy era. The status of radiation treatment of tuberculous skin lesions will be noted in the section on dermatologic conditions." And:

          "Tuberculous lymphadenitis, however, is a particular situation where radiation was actually a treatment of choice right up to the time when specific anti-tuberculous drugs took over the dominant role in therapy of tuberculosis generally. Lymphadenitis (chiefly cervical, though axillary and inguinal involvement has been occasionally seen, and successfully treated) is becoming a rare condition in tne United States, like other extra-pulmonary forms of the disease." In this context, cervical refers to the neck region, not the neck of the uterus.

          Elsewhere in the literature also, we have found many glowing comments in one paper or another about successful treatment of tuberculous lymphadenitis with x-ray. As a result, we continue to try to find a reliable source from which one could evaluate radiation dose to the breasts, particularly from cervical and axillary lymph node therapy with radiation.

o - Viral Infections:   Herpes Zoster as an Illustration

          Dewing at p.39:   "Herpes Zoster is a virus infection of the central nervous system which most often attacks the posterior root ganglia of the spinal nerves, but may attack cranial nerves as well. The disease is self-limited, but is usually extremely painful, and is often succeeded by an indolent post-herpetic neuralgia which may linger on for years, and be quite disabling. There is no specific medical treatment, but radiation therapy has been found empirically to produce marked symptomatic relief in most cases." And:

          "Most treatment is directed to the seat of the infection, in the posterior root ganglia, and uses conventional deep technic. However, there is a fair sized body of opinion which advocates treating the skin lesions with superficial x-ray, usually in combination with therapy to the spinal ganglia, but also sometimes alone."

          We are quite concerned about this combination therapy, since both aspects of it can lead to breast irradiation. As yet we have not uncovered a source of quantitative information on the breast-dose from the management of herpes zoster.

Part 4.   The Sterile Inflammatory Conditions:   Radiation Therapy

          Dewing deals with a mixed group of disorders, which he classes together because (a) there is a predominant element of inflammation and (b) there is no, or at most a minor, role of infectious agents in the disorder. (It turns out that peptic ulcer does not qualify on the latter.)

o - Arthritis and Para-Articular Painful Conditions

          Dewing at p.42:   "All forms of arthritis have been given radiotherapy at one time or another. In many cases results were equivocal, and the method was gradually abandoned for such diseases as gout and rheumatoid arthritis."

          Nonetheless, we would like very much to know what radiation dose might have been received by breasts, throughout the years of trial, in this effort to treat arthritis. Dewing states:

          "Today there seems to be little scope for radiotherapy in joint affections, as such. But there are a multitude of para-articular aches and pains which are often great problems clinically. A few can be pin-pointed, like bursitis or calcific tendonitis, but many defy accurate diagnosis, and may never be brought beyond the practical fact that one has a patient who has pain, call it fibrositis or what you will. After exhausting all the local injections, internal medications, ultra-sound, and diathermy, quite a few of these come to the radiotherapist's doorstep." And:

          "Not all of them can be helped, of course, but one has a duty to make a good try. I have had a patient tell me that she had gone through two years of fairly typical calcific tendonitis of the shoulder, frittering along with various ineffective treatments. It was cleared up in a few days when she fell, almost by accident, into the hands of a radiologist who recognized the situation and what might be done about it."

          Disorders such as this worry us concerning the possibility of breast irradiation. Unless great care was used with coning and collimation of the x-ray beam, treatment of various disorders of the shoulder could well have provided appreciable breast irradiation. It may prove impossible to assess this particular source of exposure, and the impossibility will contribute to underestimating the role of x-radiation in the etiology of breast-cancer.

o - Osteoarthritis and Para-Articular Pain

          Dewing at p.43:   "There will always be a group of patients with pain in or about certain joints, with negative or equivocal physical findings. The radiographs will show evidence of osteoarthritis, or other deformity residual from various types of joint damage --- e.g., trauma, infection, aseptic necrosis, or slipped epiphysis. Some of those who are not controlled by other means will be referred for a trial of radiation..... Any joint may be the site of damage and symptoms, but the commonest affected are the knees, hips, and cervical spine."

          We are concerned about the possible breast irradiation from cervical spine therapy in this situation.

o - Ankylosing Spondylitis (Marie-Strumpell Disease, von Becterew's Disease)

          Dewing at p.45:   "Therapy has been rather non-specific, however, and it was early learned empirically that radiation was remarkably effective in reducing or eliminating pain." And:   "Just what radiation does to the disease process (and how) is obscure. Certainly pain relief is real to the patient, and such relief is claimed for approximately 80 per cent of cases in most reports."

          "Treatment technic has included `wide field' therapy to the whole trunk, looking for a humoral effect, mediated through the sympathetic nervous system." And:

          "Most authors, however, have assumed a direct effect on the inflammatory process, and simply aimed their fields at the affected areas. These may include the sacro-iliacs and entire spine, or some portion of these fields, if the involvement is more limited."

          We are quite concerned that some of the cervical and dorsal spine irradiations can have provided appreciable breast-dose. A quantitative estimate of annual average breast-dose from treatment of this disorder may become possible someday.

          I can offer some comments to readers who may be skeptical about the relief of pain by x-irradiation in persons with ankylosing spondylitis, although the world-wide experience is so large, no one should really doubt it.

          When I was an intern in medicine, one of my patients with ankylosing spondylitis was admitted for another course of radiotherapy. At the end of each day on the wards, I visited this scholarly man for long discussions about many things. And of course we spoke about his ankylosing spondylitis, and the empiric status of our knowledge. I never forgot his statement:   "Try to think of spending each day of your life in severe pain for 24 hours a day, and then you will have a good idea of what my life has been for 20 years. The x-ray therapy has given me respite on more than one occasion and I am immensely grateful for the existence of this therapy."

o - Bursitis, Tendonitis

          Dewing at p.48:   "This condition enjoys a bewildering variety of nomenclature:   bursitis, tendonitis, calcific tendonitis, calcifying tendinitis ... and simply:   painful shoulder." And:   "The common denominator appears to be a sterile inflammation of more or less chronicity in muscle tendons attaching near joints, with more or less calcium deposit in the involved area." And of particular relevance to our concern with breast-irradiation:

          "The shoulder is the joint area most often affected by tendonitis (about 60 %)."

          Because the shoulder joint was the prime area treated, we have justifiable concern about breast irradiation as a result of inadequate coning and collimation, particularly in the early decades.

          With respect to efficacy of treatment, Dewing states:   "Without becoming involved in these arguments [as to efficacy], I would like to present a position that seems to me conservative:   there is the patient, in more or less pain. The experience and evidence are at least suggestive that radiation therapy relieves this pain, no matter how it acts. Does one have the right to refrain from treating? I am perfectly willing to let other (non radiation) methods be tried first, and if they work, that is fine. I get most of my patients after failure of other therapeutic attempts anyway. I believe that the risks of radiotherapy are negligible and one has nothing to lose by making an honest effort."

          We note his belief that "the risks of radiotherapy are negligible" from such treatment.

o - Tietze's Syndrome

          Dewing at p.58:   "Tietze's syndrome consists of a painful swelling of costal cartilage, with signs of (sterile) inflammation. It is self-limited and benign." Costal cartilage belongs to the ribs.

          Dewing suggests that response to radiotherapy was equivocal. We are not concerned (here) about whether or not the response was favorable, but rather our concern is that painful disease of the costal cartilages involves exactly a region which could mean major radiation dose to breast tissue during therapeutic efforts. Every additional disorder whose radiation therapy involved breast irradiation adds to the total breast-dose --- which adds to the number of radiation-induced breast-cancer cases.

o - Burns:   An Interesting Report from Romania

          At page 59, Dewing cites an unusual area of study, namely the use of x-rays to treat electrical and thermal burns. The idea was reported (1959) by two Romanian workers, with ostensibly very good results in the treatment of 30 burn cases. Says Dewing:   "They reported thirty cases of second or third degree (or mixed) burns. One third experienced pain relief after the first treatment; an additional fifteen were relieved after the second one; and the remainder after the third. They also felt that healing was hastened, and observed no keloids in this (rather small) group."

          Dewing suggests this technic is certainly interesting and deserving of further study. The logic is not so far-fetched. Dewing states:   "On the one hand there was the long-established anti-inflammatory action to recommend radiation. On the other, they [the Romanian investigators] suggested that if x-ray is useful to control keloids arising in burn scars, then it might be useful at other stages of the evolution of body response to the burn --- both immediately, and as prophylaxis against keloid formation."

          We do not know how far this idea got, but it is an indication that the radiologists of the day had a great deal of belief and confidence in the anti-inflammatory action of ionizing radiation.

o - Neuritis

          Dewing at p.61:   "Neuritis is a subject which ought, perhaps, to be subject to clear definition. In practice, however, it has been obfuscated by more or less careless overlap with other (and more ill-defined) painful conditions of the fibrositis-bursitis-tendonitis group ... Nevertheless, there is a sizable body of experience in treating neuritis or neuropathy, however empiric it may be. The technic of therapy is quite comparable to that employed for tendonitis. Results were considered good (i.e., complete or substantial relief of pain) in about 90 percent of cases."

          Dewing cites the work of Heidelman who described 139 patients (with adequate follow up) treated for brachialgia paraesthetica nocturna. "This condition was characterized by numbness, paraesthesias and pain in the hands and arms, typically occurring in middle aged females, and awakening them from sleep. Treatment was administered to the cervical and upper thoracic vertebral column, 100-150 R (air) to a 10 x 15 cm field, using conventional deep therapy." The treatment was repeated in a week, and a third dose was used if no response had occurred. Overall, Heidelman reported 37 percent completely well, and 56 percent more or less improved.

          Dewing adds:   "All of his [Heidelman's] patients had had the diagnosis of brachialgia made by excluding other etiologies, had not been relieved by other therapy, and were treated with x-ray alone."

          Such cases would certainly have experienced breast irradiation, whether AP or PA beams were used in therapy. This is a situation where many women could have been treated, and where irradiation of the breasts was never even considered. (Dewing also mentions a few other varieties of neuritis, treated by radiation to the vertebral levels corresponding to the location of the reported pain.)

o - Pancreatitis

          We suspect that some eyebrows will be lifted to have to consider pancreatitis as an inflammatory condition to be treated with radiation. But it clearly was regarded as a subject for consideration. The rationale is provided by Dewing at pp.62-63:

          "Pancreatitis is a condition without specific therapy, in which pain is a conspicuous feature. Reasoning by analogy from the known sensitivity of the inflamed parotid gland to radiation, many investigators have speculated on what might be done with radiotherapy for inflammation of the somewhat similar tissue of the pancreas. Treatment is uniformly with conventional deep technic, 200 Kv, 1.0 mm.Cu HVL." Three series are cited by Dewing:

          (1) Morton and Widger (1940) gave individual doses in the 50-100 R range to the pancreas, every one to two days for four to five exposures. "They [Morton and Widger] felt response to this therapy was quite encouraging."

          (2) "Levi and Engle (1950) cited 28 cases treated rather `lightly' with 75 R (air) to a 15 x 15 cm. anterior epigastric field twice, with a twenty-four hour interval. They reported definite clinical improvement which lasted hours to days, but did not appear to alter the overall course of the disease."

          (3) "Heacock and Cara (1954) described fifty-three cases given a regular course of 200 R (air) daily for three doses to an anterior abdominal 15 x 15 cm. field. Of their cases, seven required a second course some weeks later, four were given a third, and one received a fourth course. They claimed a good result in thirty-three patients, fair response in an additional fifteen, and poor or no benefit in the remaining five. Their conclusion was that radiation therapy given early enough was effective in counteracting the inflammatory process, and would abort abscess formation and other complications, as well as the chronic state of the disease."

          Pancreatitis is a serious disease. It took some bravery to suggest treating it with x-ray. Our concern is for the scattered radiation from those anterior abdominal fields. How much of that radiation dose got to breasts depends upon how well collimated the beam was and how much external scatter was present. From some of what we have seen in the pre-1960 period, we would have to wonder seriously about how well that beam was controlled.

o - Peptic Ulcer

          Again, those only recently familiar with medicine may find it incredible that peptic ulcer should be treated by a regimen which aimed at shutting down the acid-producing mechanism of the stomach. But that is exactly what was done. We have personally reviewed many of the major papers on this subject, and can vouch for Dewing's description of the seriousness with which this approach was taken.

          We do not know, from phantom studies or other studies, what the dose was to breasts of treated women, but considering the dose delivered to the stomach, we would have to worry a great deal about that problem.

          Dewing (at p.63) claims a place for radiation:   "The primary treatment of peptic ulcer is medical (and perhaps psychiatric). There are also definite indications for surgery, of course. Between these, however, radiation has a definite place as an adjunct." And:

          "The rationale of radiotherapy in peptic ulcer is happily simple and clear-cut:   suppression of hydrochloric acid secretion by the gastric glands. That this effect is produced by a tissue dose of the order of 2000 R has been thoroughly documented experimentally. Thus one can dismiss the older literature which aimed very light doses at the sympathetic ganglion chains, and critical articles by persons who gave excessive doses of 4000-6000 R, and ran into complications."

          Alerted by Dewing to this use of radiation therapy, we examined several other sources directly. In order not to interrupt the selections from Dewing, we will return to peptic ulcer in Part 5.

o - Thyroiditis

          Dewing refers to two varieties of thyroiditis for which radiation therapy has a role:   Subacute Thyroiditis and Hashimoto's Struma.

Dewing on Subacute Thyroiditis (p.69)

          "Quite a few authors have reported very encouraging results from radiotherapy in recent years, and Crile even lauds radiation as the method of choice." (The name of George Crile, Jr. is akin to magic in the field of thyroid disease.)

          Several regimens are cited by Dewing:

          Osmond and Portmann (1949) reported on 55 cases. The course consisted of 100-150 Roentgens (air), directed to a single 10 x 10 cm field encompassing the thyroid gland, and repeated every two days for four to six exposures, depending on the response of the inflammation.

          Crile and Rumsey (1950) gave daily doses of 100-150 Roentgens (air) to 35 patients, and used a single field. They fixed upon 800 Roentgens as an optimal average total dose, and felt that above 1,500 Roentgens, there was some danger of impairing thyroid gland function. Fourteen of their cases had a complete remission in one week, most of them within two weeks. Five cases required a second course of treatment after evaluation at six to eight weeks.

Our Comments

          We are concerned about there being a dose to some breast tissue, from external scatter, from lack of coning. We would feel much more comfortable about dismissing the possibility of appreciable breast-dose if some phantom data were available.

Dewing on Hashimoto's Struma (p.70)

          Dewing suggests that Hashimoto's Struma recommends itself to radiation therapy because of the predominance of lymphocytic infiltration, and the known sensitivity of the lymphocyte. He lists several regimens:

          Means (1948) used right and left fields, and gave 100 Roentgens (air) to each on alternate days until a total of 400 R to each field was reached. Allen and Reeves (1951) used 100-150 R (air) every two days to a single field up to a total of about 1,000 R to the gland. Bromley (1955) cited Crile (1948) suggesting a maximum total dose of 1,500 Roentgens for this disorder. Bromley used a dose of 2,000 Roentgens (tissue) in two weeks and was enthusiastic about this therapy.

          We retain our skepticism that the dose to the breasts was really negligible.

Part 5.   Radiation Treatment of Peptic Ulcer:   Additional Authors

          We return to the issue of radiation therapy for peptic ulcer, because of the high doses employed and the probability that the breasts received some exposure. Below, we present data and comments from three sources supplemental to Dewing.

o - The 1951 Report by Ricketts and Palmer

          William E. Ricketts and Walter L. Palmer wrote "Radiation Therapy in Peptic Ulcer," which was Chapter 34 in a book devoted to the clinical aspects of peptic ulcer. At page 381:

          "The result depends in part upon the technic used, the amounts of irradiation given, and the individual susceptibility of the organism. The portals selected are opposite each other, one located in the left hypochondrium and the other in the left costolumbar region. The size of the irradiated area should be the smallest possible to include the body and the fundus of the stomach, 13 by 13 cm. is adequate. The location, size, and configuration of the stomach should be determined fluoroscopically and the portals altered accordingly. The treatments are given daily; the portals are treated alternately. The total depth dose, as calculated in a plane one third of the distance from the anterior wall to the posterior wall, varies from 1600 to 2400 roentgens in a period of twelve days; this has been found to be perfectly safe."

          We note both the claim that the therapeutic dose was "perfectly safe," and the use of fluoroscopy in order to position the portals. At page 385, Ricketts and Palmer state:

          "In a series of approximately 1000 patients treated during the past twelve years, the development of malignant degeneration of the stomach or skin has not been seen; in fact, aside from the transitory and usually moderate nausea with dislike for milk and antacid especially, the side effects have been negligible. There has been no clinical evidence of injury of adjacent organs such as the liver and pancreas, except for one initial case in which the radiation was given at too rapid a rate. In a series of twelve patients subjected to electrocardiograms for periods of six weeks, no evidence of myocardial injury was detected." And:

          "The incidence of healing [of the peptic ulcer] following adequate amounts of irradiation together with standard antacid medical management is usually above 90 percent. The length of time required for healing varies, but in most patients it occurs within ninety days. There is evidence of a direct correlation between depression of acidity and the healing of the ulcer." And:

          "There is no correlation between the age or sex of the patients and the effect of irradiation, nor among these factors, the duration of symptoms, and healing."

Our Comments on the Ricketts-Palmer Statements

          We note that their claim of no side-effects covers a maximum follow-up time of only 12 years, and an even shorter average follow-up time.

          Our concern here is about breast irradiation. In 1951, that was not their concern at all. So of course they provide no phantom study to establish what dose an average female breast would get from the beam during such treatments. We wonder, for the period before 1951, whether the coning, the collimation, the aiming of the beam were really so accurate as to mean that breast-dose from such therapy would have been negligible. The claim is made of an irradiated area 13 by 13 cm (about 5 x 5 inches). How well was this really achieved? A phantom study would have helped a great deal.

o - The 1956 Paper by Carpender and Co-Workers

          In 1956, the American Journal of Roentgenology and Radium Therapy published "Radiation in the Therapy of Peptic Ulcer," by J.W.J. Carpender and colleagues. Data cited below are from pages 374 and 375:

          This study of gastric ulcer included 116 patients observed during the period of 1937 to 1954. The patients with duodenal ulcer were the 113 treated in 1945 and 1946. In the gastic ulcer patients, the total depth dose varied from 1,100 to 2,930 Roentgens. Most of the patients received 1,600 to 1,700 R. The patients with duodenal ulcer all received 1,600 to 1,700 Roentgens depth dose to the body and fundus of the stomach.

          The two-portal technic was used, as was the case in the Ricketts-Palmer series. Carpender et al report (p.378):

          "A reduction in gastric acidity in most patients for varying periods of time has been demonstrated with achlorhydria also for variable periods of time in a small number of patients. In no instance did an ulcer fail to heal when achlorhydria was produced for three months or longer, nor was there recurrence during such a period of achlorhydria."

          So this study of 229 additional patients with peptic ulcer confirms the broad finding of the Ricketts and Palmer study.

o - The 1957 Study by Levin and Co-Workers

          In 1957, the journal Gastroenterology published the results of a large study by Erwin Levin and colleagues entitled "Observations on the Value of Gastric Irradiation in the Treatment of Duodenal Ulcer." Their paper presented the results in 723 patients with duodenal ulcer treated with radiation and observed for 5 to 18 years. The dose used in the most recent period (1948-1950) was 1,600 to 1,700 Roentgens to the gastric fundus, with the use of 13 by 13 cm portals (p.43). Their conclusion (p.48):

          "Roentgen irradiation in moderate amounts to the acid-secreting areas of the stomach constitutes a safe and valuable adjunct in the treatment of duodenal ulcer."

          Another optimistic assertion about safety, of course.

Our Comments on the Combined Studies

          It appears that hypochlorhydria and achlorhydria were achieved in all the studies, and that ulcer healing accompanied reduction in acid production.

          Perhaps the aiming of the x-ray beam and its restriction were very good. We certainly hope so. Before MacKenzie's 1965 paper, it is not surprising that none of the studies did measurements of actual breast-dose with phantoms. So the breast-dose is an open question. And it is potentially consequential.

          Large and favorable studies were coming out of several institutions. The treatment was declared "safe." Even "perfectly safe." If radiation therapy for peptic ulcer was widely used for a while, it would make quite a difference if it delivered an associated breast-dose per patient more like 100 milli-rads, or more like 100 rads. Could it have been 50 or 100 rads?

          At this time, we do not know. There is no entry whatsoever in our Master Table for annual average breast-dose from this source.

Part 6.   The Combined Frequency of Many Treated Disorders

          This chapter presents a spectacular array of benign diseases treated with radiation therapy. All or almost all of them may have contributed breast-doses not evaluated in our Master Table.

          We were startled by a statement in the Introduction to Dr. Dewing's book (p.ix):

          "The experience of many of us is that benign treatments may account for as much as 50 per cent of the volume of clinical radiotherapeutic practice. This proportion is very apt to reflect the interest of the radiologist. He can build a practice, or let it run down, by the energy (or the lack of it) with which he sets his talents at the disposal of his referring colleagues."

          If radiotherapy of benign diseases could account for half of the "volume" of clinical radiotherapy practice in 1965, such a high fraction --- though apparently not common in 1965 --- suggests that breast-irradiation due to such treatments in the 1920-1960 period may have produced an annual average breast-dose appreciably greater than what we were able to evaluate in our Master Table.

          This concern is fortified by the widespread and very careless use of x-ray equipment by non-radiologists (see Chapters 31 and 32, for example) and by the so-called "wasted radiation" from unnecessarily large areas of exposure (Chapter 23, Part 2), and by the fact that even some beauty-shop operators were using radiation for non-diagnostic purposes (Chapter 26).

          Moreover, the combined frequency of the disorders reviewed in Parts 3, 4 and 5 must have been quite high. Even individually, some of them may not have been negligible, as contributors to breast irradiation. Is anyone in a position to rule out radiation treatment just of sore shoulders, for example, as a significant but unevaluated source of breast-irradiation? Until such possibilities can be ruled out, one by one, on the basis of some real evidence, they should not be dismissed too promptly on the basis of wishful thinking.

          Even though our Master Table presently excludes breast-dose from the therapies reviewed in this chapter, we already know this:

          Past radiotherapy of benign diseases has had an unintended consequence:   It is a cause of radiation-induced breast-cancers. We state this again, not as a criticism, but as a sobering reminder about unintended long-term consequences from actions which superficially may appear sensible.

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