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Radiation Therapy in Dermatology
Radiation Therapy in Dermatology EDWARD N. BURKE, M.D.* GEORGE LEVENE, M.D. **
days after the announcement of the discovery of x-rays, E. H. Grubbe, a manufacturer of vacuum tubes, but later a physician, exposed a patient with cancer of the breast to x-ray.l He did this, empirically, at the suggestion of a physician. The following day he treated a patient with lupus vulgaris. The interest and enthusiasm following the discovery of x-ray led to frequent overexposure of the skin. The result was a dermatitis of the exposed portions of the body and epilation of the hairy parts. As more of these findings were reported in the literature, the stage became set for the application of x-ray to the treatment of skin disease. Having read of the epiIating effect of x-ray in the American literature, Leopold Freund, in January 1897, reported the success of epiIating a large hairy nevus on the back of the neck of a young girl,2· 3 His technique was an exposure of two hours daily over a period of ten days. His report spurred the use of x-ray in dermatology and, shortly thereafter, the literature contained reports of its use for almost every type of skin disease. From 1900, the use of x-ray in the treatment of diseases of the skin has been an accepted form of therapy. It is an extremely useful agent which, in the hands of an expert, is safe and efficient. TwENTY-THREE
TECHNICAL ASPECTS
Two sources of radiation are commonly employed, namely x-ray generators and radioactive materials. The radiation produced by x-ray generators is of much longer wavelength than the gamma radiation of radium. X-rays produced in the vicinity of.i2000 kv. approaches the quality of radiation from radium. Radioactive elements produce, in addition to gamma rays, alpha and beta rays. From the Department of Radiology, Massachusetts Memorial Hospitals and Boston University School of Medicine, Boston. • Assi8tant Radiologist, Massachusetts Memorial Hospitals; Assistant Professor of Radiology, Boston University School of Medicine •• Chief, Department of Radiology, Massachusetts Memorial Hospitals; Professor 0/ Radiology, Boston University School of Medicine
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Bllrl~e,
Oeorge Levene
Radiation Available for Treatment Alpha Rays. These arc eorpusculnr radiation;; produced by the disintegmtioll of a radioactive clement. They are similar in composition to the nuclei of helium atoms. Alpha rays are of large size and produce a profound biological effect in tissue. Their ability to penetrate is limited and they are completely arrested by a sheet of paper. They are of no practical value in therapy. Beta Rays. Beta rays are corpuscular emanations which are electrons. They may penetrate tissue up to 1 cm. in depth and thus are of limited value in therapy depending upon the type of disease and its depth. Beta rays may be filtered out of a beam by the use of 2 mm. of brass, 1 mm. of lead or silver, or 0.5 mm. of platinum or gold. Gamma Rays. These are electromagnetic waves traveling with the speed of light, having a shorter wavelength than x-ray and possessing great power of penetration. They are found in the disintegration of radioactive elements or in the radiation produced in the vicinity of 2000 kv. X-rays. X-rays are electromagnetic waves produced by the sudden arrest of high velocity electrons. They are invisible, travel with the speed of light and are not influenced by a magnetic field. A beam of x-ray is heterogeneous, containing rays of varying wavelengths. The most penetrating rays are those with the shortest wavelength. Grcnz rays are x-rays produced at 10 kv. They are of very long wavelength. Their penetration is so limite([ that "'5 per eent of the rays are absorl.lc(l in the first millimeter of skin.4
Apparatus
Several factors come into consideration in the choice of apparatus for treatment. These are availability, quality of radiation desired, the type and extent of the lesion to be treated, and the control of the radiation. The most important factor is familiarity with the equipment at hand, its range of usefulness and its limitations. The most common type of apparatus in use today is the superfic'ial therapy unit operating at 50 to 140 kv. and 4 to 15 ma. at a relatively short target skin distance of 20 to 25 cm. Most radiologists and dermatologists have fixed settings for use with specific diseases depending upon the quality of radiation desired and the quantity of radiation to be delivered. Because of the superficial location of most skin lesions, a voltage of 50 to 100 kv. is USel[ at from 4 to 8 ma., unfiltered. If greater depth dose is desired, a filter of from 1 to 3 mm. of aluminum is added. Other types of radiation may be used. The beryllium window tube is gaining in popularity with many dermatologists because of its great versatility." It has an extremely high output of soft radiation and an effeetive mnge from the grenz ray to the superficial x-ray type of beam. A voltage of 10 to 100 kv. may be used. Contact therapy6 has been found useful in the treatment of superficialloealized lesions of the skin such as superficial skin carcinoma or benign keratoses. It has a short target skin distance and a high roentgen output. Because of its rapidly diminishing depth dose, it may be used safely over the skin, overlying or close to the eye, the epiphyses of bone in children, the skin overlying cartilage of the ear or nose. It operates at high intensity, requires a short treatment time, and administers adequate and homogeneous radiation to the desired areas with a minimum of radiation to the deeper placed structures.
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Radium
Radium therapy is limited in use to the treatment of localized disease. X-ray therapy has to a great extent supplanted it. Its case in application to young and uncooperative patients is a major advantage. Radium emits alpha, beta and gamma rays. Radium is used in the form of plaques, needles or see?s. A full-strength radium pl~que is one which contains 5 mg. of radIUm element per square centlmeter. The most widely used type of plaque is a half-strength plaque containing 2)5 mg. of radium per square centimeter of active surface. Several types of screens or filters are used to remove part or all of the beta rays: aluminum, which allows beta radiation to penetrate, and 2 mm. of brass which ftlters out the beta and allows only the gamma radiation to penetrate. The plaque is held in contact with the skin and when a 1 mm. aluminum filter is used it produces an erythema after a treatment time of 15 to 20 minutes. If a lesion is 3 to 4 mm. in thickness, 2 mm. of brass may be used m; a filter, and the le::;ion treated with the gamma radiation of radium. Radium needles for surface or interstitial application may be placed ill flat applicators, for surface use, or used directly as needles. One to 10 mg. needles arc most commonly employed. Radon, a gaseous emanation produced in the breakdown of radium, may be made into an ointIlH'nt for surface application or put into small metallic capsules for interstitial applications as seeds. Quality of Radiation
The quality of radiatioll is the hardlleHH or softness of the x-ray beam. It is expreHscd aH the half-value layer of copper, aluminum or other substance uscd as an ahsorhent. It is that amount of added filtration, either aluminum or copper, which will absorb half of the radiation of the incident beam. The quality of radiation is influenced by the kilovoltage, target-skin distance, and filtration. 7 Increasing the kilovoitage produces harder, more penetrating rays. Increasing the target-skin distance makes use of distance in di~tiipating the softer rays, and a greater proportion of hard rays will be present in the incident beam. Addition of filtration removes the softer rays and allO\ys only the harder rays to pass, again increasing the proportion of hard rays in the beam. Quantity of Radiation
The quantity of radiation is the amount produced at a certain point. Time, amperage, field Hize, filter, kilovoltage and distance have a direct relationship to quantity.7 It iH measured either as air dose, which is the number of roentgen produced in air at the end of the treatment cone, or as the skin dose, which is the sum of the air dose plus the backscatter on the skin surface. Quantity is measured by means of an ionization chamber. This is not a convenient instrument to use; a thimble chamber
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is generally employed. It is capable of determining the r output per minute. Quantity may also be determined by the biologic effect. It is the amount of radiation required to produce a faint pink erythema on 1 square inch of skin on a flexor surface of the forearm of a young adult of fair coloring within one week's time. This dose, known as a threshold erythema dose, or T.E.D., has been used for years as a biologic measurement. An erythema dose is produced with about 300 r of unfiltered x-ray and will cause temporary epilation of the scalp. EFFECT OF X-RAYON THE SKIN AND HAIR
Treatment of benign skin conditions with radiant energy should never produce unfavorable skin reactions such as erythema. It need hardly be mentioned that the application of x-ray to remove hair from the face or other portions of the body for cosmetic purposes is definitely contraindicated. The doses which are used in superficial therapy for benign conditions are usually small fractions of erythema doses and are used at intervals which are far enough apart to avoid the possibility of an erythema by cumulative effect. Large doses of radiation are used in the treatment of malignancies of the skin, and certain irreparable changes are produced in the tumor bed and the healthy peripheral margin, which is always included in the field of treatment. All changes which are produced in tissue are the direct result of radiation acting on the cell, or indirectly by the radiation acting on the vascular supply of the cell or tissue bed. In either case, the prime causative factor in the production of their changes is the ability of the radiation to effect ionization. Cells which are most sensitive to radiation are those which are in an active stage of cellular division and are poorly differentiated histologically. This is based on the Law of Bergonie and Tribondeau, formulated in 1906, which states that "Immature cells and cells in an active stage of division are more sensitive to radiation." They showed that radiation had its greatest effect on cells whose reproductive capacity was high, cells which showed mitoses, and on cells whose morphology and function were not fixed. Cellular and Tissue Response to Radiation
Cells of the body will vary greatly in their response to radiation. Some cells are extremely radiosensitive, and will respond to small doses of radiation, while others are radioresistant and will show changes only following large doses of x-ray. The most sensitive cells in the body are the lymphocytes, the most resistant, the nerve cells, with epithelial cells occupying an intermediate position. 8 The general effect of radiation on the living cell is one of inhibition of both reproductive and metabolic capacities, a whl~h may be temporary or permanent. The individual cell shows effects after a varying time following radiation. These changes consist of clouding and granularity of
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the protoplasm, with clumping of protein. Later, vacuoles appear. There is clumping and shrinking, and irregular grouping of the chromosomes within the nucleus. Still later pyknosis and karyorrhexis will occur. In cells undergoing mitosis, mitotic division may be stopped, altered or unchanged. If the radiation was not severe, the cells resume activity IlJld normal division. However, some cells, after apparent recovery, will suddenly die. If the irradiation was severe, cells will disintegrate immediately. The effect of radiation on the skin will vary greatly with the dose delivered and the dose absorbed. 9 , ID, 11 The dose and absorption are dependent upon the quantity, quality, size of the field, and individual sensitivity. When skin surfaces are exposed to radiation, the germinal elements of the skin, including the hair follicles, demonstrate the first changes. These sensitive cells die immediately or shortly after exposure in abortive reproductive changes. The superficial epithelial cells are not affected but, following constant normal desquamation, they are not replaced and the epidermis becomes thin. There is often edema and leukocytic infiltration in the intercellular spaces. If the reaction continues, the continuity of epithelium is lost. When the dermal papillae have been exposed, re-epithelialization proceeds from the hair follicles, sweat glands or periphery. The re-formed skin is thin, the papillae flattened, and there are fibrotic changes in the dermis. The effect of radiation on the hair is of sufficient interest to warrant special consideration.l2 The hair of the scalp is least resistant to radiation, and is followed in order by the hair of the beard, axilla, pubis and eyelashes. Ionizing radiation may affect hair color and growth by its action on the papillae. Regrown hair may be darker and curlier than the original. Graying of regenerated hair has been reported. Following large doses of radiation, mitoses are absent in the follicular matrix and there is condensation with the formation of irregular clumps of melanin in the matrix. The trichohyaline layer disappears. The hair bulb becomes misshapen, papillae atrophy and become relatively avascular. The follicle accumulates keratinous debris. The glassy sheath becomes thickened; the sebaceous glands atrophy; the more resistant sweat glands may become atrophied and vacuolized. By the sixth week there is evidence of regeneration. Gross Skin and Hair Effects9 , ID, 11
If the dose has been slight, no change will be apparent. If the radiation is greater a harmless erythema may appear and disappear in a short time. With a greater amount of radiation, erythema is produced within a week or ten days. This is associated with epilation of the hair, included in the field, within three weeks. Epilation in this case is temporary and regeneration of hair is complete in three or four months. When an erythema is followed by tanning, the pigmentation is either spotty or
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diffuse. It appears within one month following treatment from a gradual alteration of the erythema and may last indefinitely. In the Negro or dark skinned persons, depigmentation may occur (Fig. 199). The pigmentation produced with protracted therapy gradually becomes deeper in color with scaling and fissuring of the skin. This is the stage of dry epidermitis. With still larger doses of radiation, edema, vesiculation and superficial ulceration will occur, the stage of wet epidermitis. These reactions resolve slowly and require from several weeks to several months for healing, depending upon the extent of the injury and the degree of the
Fig. 199. Depigmentation of skin following deep radiation therapy, associated with atrophy and telangiectases.
reaction. Epilation which follows this type of reaction is permanent. An epilation persisting longer than six months is indicative of permanent epilation. If the radiation is more intense than the above, ulceration and necrosis will follow. The tissues pass through accelerated reactions described above or develop a dry necrosis, in either case eventually terminating in ulceration. Healing in this stage, if indolent ulceration does not follow, comes from the periphery and will take months before complete regeneration has occurred. The delayed, or chronic effects of radiation depend upon the dose delivered, the duration of the process, the quality of radiation, and the individual susceptibility. Telangiectases follow severe, but may follow mild, reactions, such as an erythema. They may appear in weeks or
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months after exposure and are usually permanent. Atrophy is a common sequel to overexposure and is often accompanied by wrinkling and parchment-like changes in the skin. Occasionally deep scarring will develop due to changes in the underlying dermis. Other chronic changes are atrophy or'Pdestruction of the sebaceous and sweat glands, longitudinal ridging: fissuring or loss of the nails, and retardation of the nail growth. Verrucal forms of acanthosis, keratoses, and the formation of squamous and basal cell carcinoma or highly anaplastic carcinoma are known to develop as late sequelae (Fig. 200).
Fig. 200. Malignant changes in the skin of the hands following radiation therapy for a benign skin disorder many years previously. (Courtesy of Dr. Herbert Mescon.)
Tissue Response13 • 14. 16
There is much speculation as to the exact mechanism.of the effect of ionizing radiation on tissue. It seems probable that the action is not due to a single factor but to many factors. It is known that the irradiation of water will produce peroxides and that cells have a high water content. Hydration of cells favors radiation response, dehydration inhibits it. It is known that small amounts of peroxide are lethal to the enzyme systems of cells, particularly those containing the sulfhydryl radical (-SH). Cells contain certain large protein molecules which are vital to metabolism. It is possible that radiation by its direct effect on the key molecule can alter it so that it is incapable of performing its vital function. Oxygen deficiency, diminished blood supply and certain chemicals, e.g., cystein, tend to increase resistance to radiation. The practical application'.of this is immediately evident. Anemia, dehydration and dietary deficiencies should be corrected for the most favorable radiation response.
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PRINCIPLES OF TREATMENT
Radiation therapy properly given is considered an art as well as a science. The amount of radiation which is given is dependent upon the type of disease, the stage of the disease, and the patient's response to the radiation. For example, rosacea with telangiectases is not ordinarily treated by radiation. However, when this is accompanied by oily skin and acneform lesions, treatment is given to the point of clearing of the lesions. In years past the use of x-ray was empirical and occasionally indiscriminate. Today it is known that there are very few diseases which may be cured by radiation, but there are many diseases which may be helped by its proper use. If a skin disease fails to respond to conservative therapy or topical applications or general treatment, radiation therapy is prescribed if it is a responsive disease. Sufficient experience has accumulated to show that no permanent harmful effect to the skin from properly applied radiation occurs. Sulzberger, Baer and associates have shown in a large series followed for 28 years that no undesirable sequelae were present when 1000 r or less were used in factors commonly employed for benign skin conditions. I6 , 17 When 1000 to 2630 r were used, about 1.5 per cent of patients showed mild skin changes. There is no evidence that radiation given up to 1400 r, using techniques commonly employed, will produce undesirable skin changes. Treatments may be fractional, subfractional or intensive, depending upon the amount given, and they are given daily, twice weekly, weekly, or at longer intervals. Fractional treatment is the administration of small amount of x-ray, generally one-quarter of an erythema dose, at short intervals of time, usually weekly; the output is generally 75 r. Subfractional treatment is an exposure smaller than fractional. It is usually one-half of the fractional, 35 to 50 r. This is the type of treatment given to children or where treatment should proceed cautiously. Intensive treatment is wben one or more erythema doses are given in one sitting or over a short period of time. This is usually used in the treatment of malignancies of the skin. Generalized Dermatoses
The body is divided into areas to be treated. Typical areas are the head, arms, anterior body, posterior body, and legs. One area may be treated daily but the same field should not be treated more than once a week. The areas may be subdivided into smaller fields for ease of treatment and uniformity of dosage. The treatment area is carefully shielded by lead rubber sheeting for large areas, or lead foil for small areas. When large areas of the body are to be treated, it is important that the patient's
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blood be checked before treatment and at intervals during the treatment. Anemia and leukopenia have been found to occur.IS Head. The head is divided into five areas, frontal, occipital, vertex, and two parietal areas, in a manner similar to that used for epilation which will be described later. The eyes, eyebrows and the face, if not involved, should be protected. Arms. The arms are treated by using three anterior and three posterior areas. The arm and forearm are divided equally into these areas. If the hands are involved they should be treated as separate areas, anteriorly and posteriorly. The fingers should be spread apart during treatment. The hand, as well as the arm should be treated separately. T~unk. The trunk is divided into four anterior and four posterior areas. Two of the areas are over the chest, and two are over the abdomen. Posteriorly, two areas should be over the scapulae, and two over the buttocks. Legs. Six areas are treated. Three areas, equally divided, are over the anterior surfaces of the legs and three over the posterior surfaces. The feet should be treated as separate areas, on the dorsal and plantar surfaces, and the toes should be held apart with cotton pled gets or cork. In treating the upper legs, the testes should be well protected. Each leg is treated separately. SPECIAL AREAS. Face. The eyes, eyebrows and hair are protected by suitable shielding. Three portals may be used, two lateral and one central. If there is little central involvement, only two lateral portals are necessary as there will be some central overlap. All other areas such as chest should be shielded with lead rubber. Axilla. The patient is placed on his side with the arm extended over the head. If the axilla is not a flat surface, the target skin distance may be increased to 30 cm., and a more homogeneous spread of the radiation will be obtained. It should not have to be mentioned that the therapy unit should be calibrated for this new distance if it is used. Gluteal Crease. The patient may lie either in the knee-chest position, assume the lithotomy position, or a prone position with the legs extended. The patient may be able to hold the natal crease apart, or strips of adheRive tape may be used to hold the buttocks apart. The spine should be protected, and the genitals should be well shielded.
Localized Patches
Localized patches of disease are treated after careful shielding of the normal surrounding skin. The protective shield may be made of lead rubber, lead foil, or other type of protective material having a lead equivalent sufficient for the kilovoltage of radiation used. When small lesions are treated, the lead foil may be cut to fit the lesion; the use of cork borers has been described to cut the lead, or it may be cut with a knife or scissors. Epilation. Several different techniques have been described for epilation. The Kienbock-Adamson technique is a safe and efficient method and has been used for many years with very satisfactory results. It is based on the principle of overlap radiation, and as a result there is some unequality of the dosage on the surface of the scalp. Strauss and Kligmanl9 have measured the amount of radiation that the scalp actually receives during an epilation. They have found that there are several
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areas on the scalp which receive a dosage of over twice the radiation administered at one treatment point. They state that the dosage which is necessary for permanent alopecia is greater than 1000 r. Total epilation of the scalp is to be preferred to the treatment of small focal areas of disease. To epilate a small area, it is carefully shielded with lead foil and 300 r unfiltered radiation is given at 100 kv. The Kienbock-Adamson technique20 consists in marking out 5 points on the scalp. These points are located approximately as follows: Point A is located 31 to 1 inch in front of the vertex. Point B is 31 to 1 inch inside the hairline over the frontal bone. Point C is located 1 to 2 inches inside the posterior hairline over the occipital bone. Points D and E are located 1 to 131 inches above and
c
Fig. 201. Diagramatic sketches to show the focal points in the Kienbock-Adamson technique. Left, Lateral view. Right, The relationship of the central portal to the lateral, anterior and posterior portals. slightly in front of the ears. The most important factor is to have the points between 431 to 531 inches apart. A most satisfactory method is by means of a knotted string, in which two knots are between 431 and 531 inches apart, depending on the size and shape of the skull. The points are then marked off on the closely clipped scalp so that the distance between points are equal (Fig. 201, A, B). Each point is treated with 300 r of unfiltered radiation at 20 cm. target-skin distance, using 100 kv. The tube is centered so that it is perpendicular to the planes of the other fields. The head should be supported with sand bags and the patient positioned for optimum exposure. In the treatment of uncooperative children, it has been necessary on occasion to use sedation, or when sedation alone has been unsuccessful, general anesthesia in the form of rectal Pentothal, or other general anesthestic. TREATMENT OF SPECIFIC DISEASES
Acne Vulgaris This disease is characterized by oiliness, comedone, pustules, papules and scarring. Radiation should not be used in the acute form or until
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other adequate measures have been employed. It should be used in the chronic indurated type characterized by cystic changes or hypertrophic scars, and in the type with large comedones or accompanied by oily seborrhea. Sixty to 75 per cent cure of stubborn cases may be expected. 22 Treatment is 75 r unfiltered radiation given weekly to each area for six to eight weeks. Some recalcitrant cases will require a total amount of 1400 r given in fractionated treatments. In treating thick lesions, 1 to 2 mm. of aluminum should be used. Acne Varioliformis
A temporary response may be obtained in this condition. Topical remedies are of great value but they may be supplanted by small doses of radiation. The treatment is 75 r weekly of unfiltered radiation. Boils and Carbuncles
The development of antibiotics has made the treatment of boils and carbuncles by radiation obsolete. However, the pain associated with these conditions may be relieved by one dose of 250 to 300 r filtered with 1 to 3 mm. AJ.23 Dermatitis
Atopic. Atopic dermatitis in infants and very young children should not be treated by x-ray. The disease tends to be recurrent and care in treatment is advised. Treatment in older children and adults consists of subfractional treatments of 35 to 50 r unfiltered radiation at weekly intervals. Contact. Radiation has little effect on the acute stages of contact dermatitis,24 but it is helpful in relieving the itching. In the chronic lichenified type of dermatitis, 75 r unfiltered radiation weekly for four to six treatments will help. Infectious. X-ray should not be used in the acute stage but may be helpful in the chronic stage. Seventy-five r unfiltered radiation should be given weekly for six to eight treatments. Nummular. These are coinlike patches of eczema which itch and are associated with crusting and scarring. Seventy-five r of unfiltered radiation weekly will help. Crissey and Shelly25 have reported the beneficial results of x-ray in this condition in a controlled study. Seborrheic. Topical medication is preferred in this· condition. Occasionally when oiliness is excessive and there is considerable scaling, the condition may be helped by small doses of radiation. If t4ere is considerable erythema, subfractional doses of 35 to 50 r should be given at weekly intervals for six to eight weeks. The usual treatment is to give 75 r unfiltered radiati.on to the skin at weekly intervals for four to six treatments.
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Epidermophytosis
This condition responds well to fungicidal therapy. In the chronic eczematous or hypertrophic v2.rieties, several weekly fractionated treatments are helpful. Itching in the acute stage may be relieved. Treatment consists of 75 r weekly, unfiltered radiation for three or four treatments. Hem angiomas
The port-wine stain is not considered suitable for radiation therapy. Many of the hemangioma simplex, or strawberry marks, will spontaneously fibrose during the first year of life. There are other suitable methods of treatment such a~ sclerosing injections or the application of solid carbon dioxide. If a strawberry mark enlarges, or if it is located in a conspicuous area, treatment may be given by x-ray, contact therapy, or radium. X-rays may be used giving 200 to 250 r every six weeks, halting the treatment when the first sign of regression is noted, but not exceeding four treatments. It should be re-emphasized that treatment over the epiphyses, eyes and gonads should be avoided. Because of the ease of application, radium is well suited to the treatment of hemangiomas. A half-strength plaque of radium will produce an erythema of the skin if applied for 15 to 20 minutes. A dosage of less than an erythema, or ten minutes of treatment time, may be administered, using a half-strength plaque of appropriate size. The earlier in life the treatment is given, the more favorable the result. Usually two or three treatments at monthly intervals are required. Cavernous hemangiomas are best treated during childhood because of the fibrotic component which becomes apparent in young adult life. Two hundred to 250 r may be given by superficial x-ray at intervals of six weeks for a total of six to eight treatments. If the angioma is thick, appropriate filtration with aluminum should be used. Interstitial treatment with radium needles has been employed in this condition with excellent results. Radium plaques have also been used for this type of tumor. A double-strength plaque with 2 mm. of brass filtration may be used at 0.5 cm. If the lesion is thick, a distance of 1 cm. is recommended. A double strength plaque should be applied for 1%: hours. A half-strength plaque 2 by 2 cm. in size at the same distance requires seven hours. The dose may be repeated in three months if necessary. Hyperhidrosis, Bromhidrosis and Chromhidrosis
The technique in the treatment of these diseases is one which is designed to produce inhibition of the sweat glands. This is accomplished by giving suberythema doses of 225 to 250 r at intervals of three to four weeks with a filter of 1 mm. of aluminum. A total dose of 1400 r should never be exceeded. Dryness of the skin due to inhibition of the more sensitive sebaceous glands will occur.26 Only localized areas of hyperhidrosis should be treated. The generalized type is not suitable for treat-
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ment, and the scalp and face should be excluded from treatment. The skin should be carefully watched during treatment and the production of erythema is to be avoided. Keloid
The chronic organized type of keloid will not respond to radiation. Young keloids less than 1 cm. in thickness will respond to suberythema treatments of 250 to 275 r at intervals of three to four weeks. Daily massage of the keloid is helpful and gives a sense of accomplishment to some patients or parents. Following surgical excision of keloids, a single dose of 300 to 400 r may be sufficient to prevent recurrence. Thick keloids should be treated with radium or by x-ray using filtration of 3 mm. of aluminum. The gamma rays of radium produce satisfactory results for the thicker lesions and the beta rays produce satisfactory results for the thinner lesions.. Lichen Planus
The acute and the subacute stages of the disease respond well to medical treatment, and fairly rapidly. When itching is associated with the acute stage it may be helped by the administration of 75 r weekly for four to six treatments. When the disease is generalized, the body is divided into five areas-head, trunk (two areas), arms and legs-and one area is treated daily with 75 r unfiltered radiation. The same area is not treated more than once a week, and the treatments are for a period of four to six weeks. NeuroderIllatitis
Radiation is helpful in relieving the itching associated with the skin reaction. The accompanying skin reaction is rarely helped. The symptoms during an acute exacerbation of the disease may be helped by small fractionated doses of x-ray. In the disseminated type it is necessary to treat the whole body. The technique for this has been previously described. The total dose should, again, never exceed 1400 r. Treatment is 75 r weekly for six treatments. It is inadvisable to treat infants or children. Psoriasis
Psoriasis will respond very well to several treatments of unfiltered radiation at weekly intervals. Radiation should not be used as a routine procedure as the disease is recurrent and the results are temporary. A careful history should be taken, particularly for prior radiation, before treatment is instituted. The subacute and chronic forms respond best. If the lesions reappear within three or four months, the treatment should not be repeated. Over-radiation should be carefully avoided. Treatment is 75 r weekly, unfiltered radiation for three to four weeks.
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Rosacea
Radiation is not indicated in the acute stage characterized by erythema and telangiectases. When accompanied by acneform changes, e.g., oily skin and pustules, x-ray given in weekly treatments of 75 r unfiltered radiation is of help. If the erythema is marked, subfractional doses should be used. Pruritus
The x-ray treatment of pruritus should not be continued for more than two or three visits. In many of our patients we have found that minute fissures or lacerations that could be seen only with a magnifying glass were the exciting cause of the itching, which disappeared very quickly with topical applications of bactericidal or healing ointments. The local treatment is accomplished by proper positioning, as previously described, and shielding of the spine and genitals. Fractionated treatments of 75 r unfiltered radiation for four to six treatments may be expected to produce good results in about half of the cases treated. Ringworlll of the Scalp
Radiation produces excellent results in tinea capitis and favus. Scarring due to disease, particularly in favus, becomes evident following treatment, and parents should be advised that the disease and not the irradiation produces this. In treating favus, the output should be increased to 350 r. The ears and face should be protected during treatment. Kligman21 has shown that in the pathogenesis of tinea capitis due to M. audouini, the infection passes through various stages. These stages are an incubation period, a period of enlargement and spread, a refractory period and a period of involution. The refractory state is a stage which develops after three to four months. It is of importance in that following epilation at this stage, reinfection will not occur, and subsequent treatment with fungicides is not necessary. For this reason it seems logical that for the first three or four months fungicides applied locally should be employed. After the development of the refractory period, epilation may be used. Kligman, in addition, points out that the oft reported frustrating failures of local epilation are due to treatment in the earlier stages before the development of refraction. Local epilation in selected cases is possible during this refractory stage. Defluvium begins in three weeks and regeneration is complete at four months. When hair begins to fall, it may be removed by using adhesive tape, or by manual removal. It is needless to state that the patient should wear a stocking cap at this time to prevent dissemination of infection. Tinea Barbae
',Tinea barbae may be cured by epilation of the beard. This, however, is a most serious procedure and permanent skin damage often follows;
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it is not a recommended procedure. Fractionated treatments of 75 r daily for a total of 400 r will often be of benefit. Erythema is to be avoided. Warts Plantar warts may be removed by the application of a single large dose of 1500 r unfiltered radiation. The best results are obtained when the wart is of the thick hyperkeratotic variety and at least part of the thick cornification is removed prior to treatment. The lesion should be carefully shielded and the treatment should not be repeated. Occasionally a filter of 1 mm. of aluminum should be used when the wart is thick and sclerotic. Verruca vulgaris is best treated by other means. It may be treated with a single intensive treatment of 1500 r. The treatment should not be repeated. Malignancies of the Skin
: An accurate evaluation of the tumor size and allowance of an adequate margin, and treatment with sufficient radiation with due consideration for healing, are basic tenets. The size of the lesion, the rate of treatment, and the total amount of radiation should be outlined before the onset of treatment. Widmann, of Philadelphia, treats basal cell and squamous cell carcinomas in the same manner, without regard for sensitivity.27 This is an excellent method, for some basal cell carcinomas are sensitive and others quite resistant, and some squamous cell carcinomas respond in the same manner. Holmes and Schulz divide lesions of the skin into small, moderate and very large lesions. 28 Small lesions of the skin, less than] cm. in size, are treated by 100 kv. x-ray. They may be treated with a single massive dose of 2400 to 3000 r, or treatment may be divided, giving 1200 I' on three successive days. If the lesions are small and shallow, 1000 I' every other day for three treatments is sufficient. If the lesions are thick, i.e., having an elevation of 5 mm. or more, 1500 I' every other day for three doses should be given. Moderate lesions having a size of 1.5 to 5 cm. are treated by 500 I' daily for a total of 3500 to 5000 1', depending upon the size and thickness of the lesion. Thick lesions should be filtered with from 1 to 3 mm. of aluminum. Large lesions greater than 5 cm. in size may be treated with 140 kv. or 200 kv. The rate of administration may be from 200 to 500 r daily. The treatment must be carefully administered due to the large treatment area, and the likelihood of poor healing or necrosis. When using 200 kv., it should be remembered that a sizeable dose is produced in the normal tissue lying at a considerable depth beneath the tumor. Damage to the brain has been reported following the treatment of basal cell carcinoma in the overlying skin. 29 The first course of therapy should be adequate so that further radiation is unnecessary. If, on follow-up several weeks after completion of treatment, an additional 1000 I' is deemed necessary, it may be given to the local area of suspicion. 27
Skin malignancies overlying cartilage of the nose or ear are best treated by surgery. Radiation by superficial x-ray in these regions may
1282
Edward N. Burke, George Levene
lead to occasional painful chondritis. In lesions about the eye, the eyelid should be most carefully shielded to avoid the production of radiation cataract or other injury. Contact therapy is of value in treating lesions about the eye, overlying cartilage, or in the region of the gonads or epiphyses. Pendergrass and Chamberlain 6 recommend contact therapy dosages of from 5000 to 10,000 r, with a mean dose of 7000 r. They use as a rule of thumb an adjustment of penetration so that "dY2" (where dY2 is equal to the half value of the surface dose) coincides with the deepest portion of the tumor plus a slight margin of safety. Radium is of great value in the treatment of uncooperative patients or as an alternative method of therapy. Because of the ease of administration and the excellent results with x-ray, however, radium has been largely supplanted. Flat or shallow lesions are treated with radium at a distance of 0.5 cm. Elevated lesions are treated at a distance of 1 cm. Filtration with 2 mm. of brass, 2 mm. of silver, or 0.5 mm. of platinum is used. Lesions less than 2 cm. in size may be treated with massive doses-6 to 8 T.E.D. (threshold erythema dose), or 6000 to 8000 gamma roentgens. Large lesions should be fractionated by giving 1000 gamma r daily, or every other day, for a total of 6000 to 8000 gamma roentgens. The use of Quimby's or Patterson and Parker's charts enables the conversion of milligram-hours of radium into gamma roentgens. CONTRAINDICATIONS
The contraindications to radiation therapy may be absolute or relative. 30 The absolute contraindications may be those relating to the patient, apparatus or operator. Blood dyscrasias, previous radiation up to skin tolerance, skin diseases which are characterized by atrophy, or which result in atrophy, disease with scarring, or when acute inflammation is present, are absolute contraindications. The use of technicians without training, or poorly trained, should not be permitted. It should not be necessary to state that a physician should set up each patient, check the filter and the other factors to be used before treatment is begun. The use of apparatus which has not been calibrated is not permitted. Failure of a condition to respond after a fair trial is an indication for terminating therapy. Relative contraindications are those in which there is a temporary impediment to treatment. They may be due to anemia, dehydration, poor nutrition, general debility or inability to cooperate. The use of strong agents such as the heavy metals, iodine, mercurochrome, mercury, sulfur, coal tar and iodoform should be avoided before, during and after radiation therapy. These agents tend to sensitize the skin to the effect of radiation and an accelerated, severe reaction will be produced. The use of any agent on the skin following radiation, except extremely bland ointments, is to be condemned. Physical agents such as ultraviolet and infra-red rays, heating pads, or exposure to sunlight will intensify radiation reaction. In addition, there are certain individuals who are extremely
Radiation Therapy in Dermatology
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sensitive to the action of radiation. They are usually persons of fair complexion who have a history of extreme sensitivity to the sun. Accurate and complete records should be maintained for protection of the patient at all times. Table I SUMMARY OF X-RAY TREATMENT OF SKIN DISEASES DISEASE
Acne vulgaris Acne varioliformis Boils and carbuncles Atopic dermatitis Contact dermatitis
Infectious eczematoid dermatitis Nummular dermatitis
Seborrheic dermatitis Epidermophytosis
TREATMENT
Fractionate, 75 r weekly Several doses, fractionate, If scalp infected, 38 r weekly by Adamson-Kiento clearing bock technique 250 to 300 r, filtered with 3 AI, 1 treatment Subfractionate. 35 to 50 r weekly 75 r, 4 to 8 treatments
75 r, 4 to 6 treatments Fractionate, 75 r weekly, 6 to 8 weeks 75 r weekly, 4 to 6 treatmenta
Fractionate, 75 r weekly. 3 or 4 treatments
Hyperhidrosis, bromhi- Fractionate, 75 r weekly drosis, chromhidrosis 225 to 275 revery 3 to 4 Keloid week"_ filtration 3 Al for thick lesions Lichen planus Hypertrophic type Neurodermatitis
PsoriasiB
ALTERNATIVE
35 to 50 r weekly, for 6 to 8 treatments. if erythema is marked
200 to 225 r filtered, monthly
COMMENT
Topical remedies are of greatest value. Will relieve pain.
Chronic types of dermatitis. Pruritus of acute stage may be helped. For use in chronic stage.
If 4 to 6 treatments do not help, do not persist. (Acute vesicular type respon:is best.) Generally not satisfactory Give up to 1500 r if necessary. Stop when blanching occurs.
75 r fractionate, 4 to 6 treatments 75 r filtered with 1 AI, up to 1400 r if necessary 75 r weekly, 6 treatments 75 r weekly
For relief of pruritus. Generally inadvisable to treat rapidly reClIrring types or
Rosacea
Pruritus Ringworm of the scalp Favus Tinea capi tis Tinea barbae Warts
75 r, fractionate, for total of 600 r 75 r, fraction ate, 4 to 6 treatruents Epilation Epilation 75 r every other day to 400 r. l'rythema is avoided 1500 r at OIle sitting; if thick filter with 1 mm. Al
38 r, fractionate, if erytherna is present
Occasional spot epilation, generally unsatisfactory Occasionally 250 r
acute stage. For pustular and oily stages.
To be used only in severe cases. Do not repeat.
REFERENCES 1. Pfahler, G. E.: Development of Roentgen Therapy During Fifty Years. Radiology 45: 503-521, 1945. ~!. Pusey, W. A.: The History of Dermatology. Springfield, Ill., C. C Thomas, 1933. 3. Glasser, Otto: Wilhelm Conrad Roentgen. Springfield, Ill., C. C Thomas, 1934.
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4. Cipolhro, A. C. allll MutsdlUlIer, A.: Absorption of Roentgen Rays by the Skin. Arch. Dermat. & Syph. 41: 87-97, 1940. 5. Cipollaro, A. C.: Beryllium Window Radiations for Superficial Therapy. Arch. Dermat. & Syph. 62: 214-221, 1950. 6. Pcndergrass, E. P. and Chamberlain, R. H.: In Clinical Therapeutic Radiology, U. V. Portman, Editor. New York, Thomas Nelson & Sons, 1950. 7. Glasser, 0., Quimby, E. H., Taylor, L. S. and Weatherwax, J. L.: Physical Foundations of Radiology. New York, Paul B. Hoeber & Sons, 1947. 8. Desjardins, A. U.: Radiosensitiveness of Cells and Tissues. Arch. Surg. 25: 926, 1932. 9. Akerman, L. V.: Cancer-Diagnosis, Treatment and Prognosis. St. Louis, C. V. Mosby Co., 1954. 10. Alien, A. C.: The Skin. St. Louis, C. V. Mosby Co., 1954. 11. McKee, G. M., and Cipollaro, A. C.: X-rays and Radium in the Treatment of Diseases of the Skin. Philadelphia, Lea & Fcbiger, 1946. 12. Liebow, A. A.: Effects Produced on Hair by Atomic Bombs. Ann. New York Aead. Sc. 53: 688-689, 1951. 13. Jung, F. T.: Physiological and Chemical Changes in Radiation Injuries. Arch. Dermat. & Syph. 64: 5.55-561, 1951. 14. Lea, D. E.: Actions of Radiations on Living Cells. New York, The Macmillan Co., 1947. 1.5. Patt, H. M.: Protective Mechanisms in Ionizing Radiation Injury. Physiol. Review 33: 35-76, 1954. 16. Sulzberger, M., Baer, R. and Borota, A.: Do Roentgen Ray Treatments as Given by Skin Specialists Produce Cancer or Other Sequelae? Arch. Dermat. & Syph. 65: 639-655, 1952. 17. Baer, R. L., Borota, A. and Sulzberger, M.: The Late Therapeutic Results Produced by Low Voltage Roentgen Rays and Other Forms of Therapy in Certain Benign Chronic Skin Diseases. J. Invest. Dermat. 19: 325-331,1952. 18. Poscher, F. and Kanee, B.: Reactions of the lIematopoetic System of Agents Used in the Treatment of Dermatoses. Arch. Dermat. & Syph. 53: 1-5, 1946. 19. Strauss, J. S. and Kligman, A. M.: Distribution of Skin Doses over Scalp in Therapy of Tinea Capitis with Superficial X-rays. Arch. Dermal,. & Syph. 69: 331-341, 1949. 20. Adamson, H. B.: A Simplified Method of X-ray Application for the Cure of Ringworm of the Scalp: Kienbock's Method. Lancet 1: 1378, 1909. 21. Kligman, A. M.: The Pathogenesis of Tinea Capitis due to Microsporon Audouini and Microsporon Canis. J. Invest. Dermat. 18: 231-246, 1952. 22. Crawford, G. M., Luis:;trt, R. H. Jr., and Tilley, R. F.: Roentgen Therapy in Acne. New England J. Med. 245: 726-728, 1951. 23. O'Brien, F. W.: The Treatment of Severe Carbuncles by X-ray. New England J. Med. 220: 917-919, 1939. 24. Kemp, T. S., and Kligman, A. M.: Effect of X-rayon Experimentally Produced Acute Contact Dermatitis. J. Invest. Dermat. 23: 423-425, 1954. 25. Crissey, J. T., and Shelley, W. B.: A Controlled Study of the Effect of X-ray Therapy in Certain Nonmalignant Dermatoses. New England J. Med. 247: 965-970, 1952. 26. Borak, J. (translated by E. T. Teddy): The Radiation Biology of the Cutaneous Glands. Radiology 27: 651-655, 1936. 27. Widmann, B. P.: Clinical Therapeutic Radiology; U. V. Portman, Editor. New York, Thomas Nelson & Sons, 1950. 28. Holmes, G. W. and Schulz, M. D.: Therapeutic Radiology. Philadelphia, Lea & Febiger, 1950. 29. Duggan, G. S., Stratford, J. G. and Bouchard, J.: Necrosis of the Brain Following Roentgen Irradiation. Am. J. Roent. & Rad. Ther. 72: 953-960, 1954. 30. Lane, C. G.: Roentgen Rays ill Treatment of Cutaneous Disease. Arch. Dermat. & Syph. 61: 426, 1950. 750 Harrison Avenue Boston 15, Massachusetts
days after the announcement of the discovery of x-rays, E. H. Grubbe, a manufacturer of vacuum tubes, but later a physician, exposed a patient with cancer of the breast to x-ray.l He did this, empirically, at the suggestion of a physician. The following day he treated a patient with lupus vulgaris. The interest and enthusiasm following the discovery of x-ray led to frequent overexposure of the skin. The result was a dermatitis of the exposed portions of the body and epilation of the hairy parts. As more of these findings were reported in the literature, the stage became set for the application of x-ray to the treatment of skin disease. Having read of the epiIating effect of x-ray in the American literature, Leopold Freund, in January 1897, reported the success of epiIating a large hairy nevus on the back of the neck of a young girl,2· 3 His technique was an exposure of two hours daily over a period of ten days. His report spurred the use of x-ray in dermatology and, shortly thereafter, the literature contained reports of its use for almost every type of skin disease. From 1900, the use of x-ray in the treatment of diseases of the skin has been an accepted form of therapy. It is an extremely useful agent which, in the hands of an expert, is safe and efficient. TwENTY-THREE
TECHNICAL ASPECTS
Two sources of radiation are commonly employed, namely x-ray generators and radioactive materials. The radiation produced by x-ray generators is of much longer wavelength than the gamma radiation of radium. X-rays produced in the vicinity of.i2000 kv. approaches the quality of radiation from radium. Radioactive elements produce, in addition to gamma rays, alpha and beta rays. From the Department of Radiology, Massachusetts Memorial Hospitals and Boston University School of Medicine, Boston. • Assi8tant Radiologist, Massachusetts Memorial Hospitals; Assistant Professor of Radiology, Boston University School of Medicine •• Chief, Department of Radiology, Massachusetts Memorial Hospitals; Professor 0/ Radiology, Boston University School of Medicine
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Edward N.
Bllrl~e,
Oeorge Levene
Radiation Available for Treatment Alpha Rays. These arc eorpusculnr radiation;; produced by the disintegmtioll of a radioactive clement. They are similar in composition to the nuclei of helium atoms. Alpha rays are of large size and produce a profound biological effect in tissue. Their ability to penetrate is limited and they are completely arrested by a sheet of paper. They are of no practical value in therapy. Beta Rays. Beta rays are corpuscular emanations which are electrons. They may penetrate tissue up to 1 cm. in depth and thus are of limited value in therapy depending upon the type of disease and its depth. Beta rays may be filtered out of a beam by the use of 2 mm. of brass, 1 mm. of lead or silver, or 0.5 mm. of platinum or gold. Gamma Rays. These are electromagnetic waves traveling with the speed of light, having a shorter wavelength than x-ray and possessing great power of penetration. They are found in the disintegration of radioactive elements or in the radiation produced in the vicinity of 2000 kv. X-rays. X-rays are electromagnetic waves produced by the sudden arrest of high velocity electrons. They are invisible, travel with the speed of light and are not influenced by a magnetic field. A beam of x-ray is heterogeneous, containing rays of varying wavelengths. The most penetrating rays are those with the shortest wavelength. Grcnz rays are x-rays produced at 10 kv. They are of very long wavelength. Their penetration is so limite([ that "'5 per eent of the rays are absorl.lc(l in the first millimeter of skin.4
Apparatus
Several factors come into consideration in the choice of apparatus for treatment. These are availability, quality of radiation desired, the type and extent of the lesion to be treated, and the control of the radiation. The most important factor is familiarity with the equipment at hand, its range of usefulness and its limitations. The most common type of apparatus in use today is the superfic'ial therapy unit operating at 50 to 140 kv. and 4 to 15 ma. at a relatively short target skin distance of 20 to 25 cm. Most radiologists and dermatologists have fixed settings for use with specific diseases depending upon the quality of radiation desired and the quantity of radiation to be delivered. Because of the superficial location of most skin lesions, a voltage of 50 to 100 kv. is USel[ at from 4 to 8 ma., unfiltered. If greater depth dose is desired, a filter of from 1 to 3 mm. of aluminum is added. Other types of radiation may be used. The beryllium window tube is gaining in popularity with many dermatologists because of its great versatility." It has an extremely high output of soft radiation and an effeetive mnge from the grenz ray to the superficial x-ray type of beam. A voltage of 10 to 100 kv. may be used. Contact therapy6 has been found useful in the treatment of superficialloealized lesions of the skin such as superficial skin carcinoma or benign keratoses. It has a short target skin distance and a high roentgen output. Because of its rapidly diminishing depth dose, it may be used safely over the skin, overlying or close to the eye, the epiphyses of bone in children, the skin overlying cartilage of the ear or nose. It operates at high intensity, requires a short treatment time, and administers adequate and homogeneous radiation to the desired areas with a minimum of radiation to the deeper placed structures.
Radiation 1'herapy 'in Dermatology
126rJ
Radium
Radium therapy is limited in use to the treatment of localized disease. X-ray therapy has to a great extent supplanted it. Its case in application to young and uncooperative patients is a major advantage. Radium emits alpha, beta and gamma rays. Radium is used in the form of plaques, needles or see?s. A full-strength radium pl~que is one which contains 5 mg. of radIUm element per square centlmeter. The most widely used type of plaque is a half-strength plaque containing 2)5 mg. of radium per square centimeter of active surface. Several types of screens or filters are used to remove part or all of the beta rays: aluminum, which allows beta radiation to penetrate, and 2 mm. of brass which ftlters out the beta and allows only the gamma radiation to penetrate. The plaque is held in contact with the skin and when a 1 mm. aluminum filter is used it produces an erythema after a treatment time of 15 to 20 minutes. If a lesion is 3 to 4 mm. in thickness, 2 mm. of brass may be used m; a filter, and the le::;ion treated with the gamma radiation of radium. Radium needles for surface or interstitial application may be placed ill flat applicators, for surface use, or used directly as needles. One to 10 mg. needles arc most commonly employed. Radon, a gaseous emanation produced in the breakdown of radium, may be made into an ointIlH'nt for surface application or put into small metallic capsules for interstitial applications as seeds. Quality of Radiation
The quality of radiatioll is the hardlleHH or softness of the x-ray beam. It is expreHscd aH the half-value layer of copper, aluminum or other substance uscd as an ahsorhent. It is that amount of added filtration, either aluminum or copper, which will absorb half of the radiation of the incident beam. The quality of radiation is influenced by the kilovoltage, target-skin distance, and filtration. 7 Increasing the kilovoitage produces harder, more penetrating rays. Increasing the target-skin distance makes use of distance in di~tiipating the softer rays, and a greater proportion of hard rays will be present in the incident beam. Addition of filtration removes the softer rays and allO\ys only the harder rays to pass, again increasing the proportion of hard rays in the beam. Quantity of Radiation
The quantity of radiation is the amount produced at a certain point. Time, amperage, field Hize, filter, kilovoltage and distance have a direct relationship to quantity.7 It iH measured either as air dose, which is the number of roentgen produced in air at the end of the treatment cone, or as the skin dose, which is the sum of the air dose plus the backscatter on the skin surface. Quantity is measured by means of an ionization chamber. This is not a convenient instrument to use; a thimble chamber
1270
Edward N. Burke, George Levene
is generally employed. It is capable of determining the r output per minute. Quantity may also be determined by the biologic effect. It is the amount of radiation required to produce a faint pink erythema on 1 square inch of skin on a flexor surface of the forearm of a young adult of fair coloring within one week's time. This dose, known as a threshold erythema dose, or T.E.D., has been used for years as a biologic measurement. An erythema dose is produced with about 300 r of unfiltered x-ray and will cause temporary epilation of the scalp. EFFECT OF X-RAYON THE SKIN AND HAIR
Treatment of benign skin conditions with radiant energy should never produce unfavorable skin reactions such as erythema. It need hardly be mentioned that the application of x-ray to remove hair from the face or other portions of the body for cosmetic purposes is definitely contraindicated. The doses which are used in superficial therapy for benign conditions are usually small fractions of erythema doses and are used at intervals which are far enough apart to avoid the possibility of an erythema by cumulative effect. Large doses of radiation are used in the treatment of malignancies of the skin, and certain irreparable changes are produced in the tumor bed and the healthy peripheral margin, which is always included in the field of treatment. All changes which are produced in tissue are the direct result of radiation acting on the cell, or indirectly by the radiation acting on the vascular supply of the cell or tissue bed. In either case, the prime causative factor in the production of their changes is the ability of the radiation to effect ionization. Cells which are most sensitive to radiation are those which are in an active stage of cellular division and are poorly differentiated histologically. This is based on the Law of Bergonie and Tribondeau, formulated in 1906, which states that "Immature cells and cells in an active stage of division are more sensitive to radiation." They showed that radiation had its greatest effect on cells whose reproductive capacity was high, cells which showed mitoses, and on cells whose morphology and function were not fixed. Cellular and Tissue Response to Radiation
Cells of the body will vary greatly in their response to radiation. Some cells are extremely radiosensitive, and will respond to small doses of radiation, while others are radioresistant and will show changes only following large doses of x-ray. The most sensitive cells in the body are the lymphocytes, the most resistant, the nerve cells, with epithelial cells occupying an intermediate position. 8 The general effect of radiation on the living cell is one of inhibition of both reproductive and metabolic capacities, a whl~h may be temporary or permanent. The individual cell shows effects after a varying time following radiation. These changes consist of clouding and granularity of
Radiation Therapy in Dermatology
1271
the protoplasm, with clumping of protein. Later, vacuoles appear. There is clumping and shrinking, and irregular grouping of the chromosomes within the nucleus. Still later pyknosis and karyorrhexis will occur. In cells undergoing mitosis, mitotic division may be stopped, altered or unchanged. If the radiation was not severe, the cells resume activity IlJld normal division. However, some cells, after apparent recovery, will suddenly die. If the irradiation was severe, cells will disintegrate immediately. The effect of radiation on the skin will vary greatly with the dose delivered and the dose absorbed. 9 , ID, 11 The dose and absorption are dependent upon the quantity, quality, size of the field, and individual sensitivity. When skin surfaces are exposed to radiation, the germinal elements of the skin, including the hair follicles, demonstrate the first changes. These sensitive cells die immediately or shortly after exposure in abortive reproductive changes. The superficial epithelial cells are not affected but, following constant normal desquamation, they are not replaced and the epidermis becomes thin. There is often edema and leukocytic infiltration in the intercellular spaces. If the reaction continues, the continuity of epithelium is lost. When the dermal papillae have been exposed, re-epithelialization proceeds from the hair follicles, sweat glands or periphery. The re-formed skin is thin, the papillae flattened, and there are fibrotic changes in the dermis. The effect of radiation on the hair is of sufficient interest to warrant special consideration.l2 The hair of the scalp is least resistant to radiation, and is followed in order by the hair of the beard, axilla, pubis and eyelashes. Ionizing radiation may affect hair color and growth by its action on the papillae. Regrown hair may be darker and curlier than the original. Graying of regenerated hair has been reported. Following large doses of radiation, mitoses are absent in the follicular matrix and there is condensation with the formation of irregular clumps of melanin in the matrix. The trichohyaline layer disappears. The hair bulb becomes misshapen, papillae atrophy and become relatively avascular. The follicle accumulates keratinous debris. The glassy sheath becomes thickened; the sebaceous glands atrophy; the more resistant sweat glands may become atrophied and vacuolized. By the sixth week there is evidence of regeneration. Gross Skin and Hair Effects9 , ID, 11
If the dose has been slight, no change will be apparent. If the radiation is greater a harmless erythema may appear and disappear in a short time. With a greater amount of radiation, erythema is produced within a week or ten days. This is associated with epilation of the hair, included in the field, within three weeks. Epilation in this case is temporary and regeneration of hair is complete in three or four months. When an erythema is followed by tanning, the pigmentation is either spotty or
1272
Edward N. Burke, George Levene
diffuse. It appears within one month following treatment from a gradual alteration of the erythema and may last indefinitely. In the Negro or dark skinned persons, depigmentation may occur (Fig. 199). The pigmentation produced with protracted therapy gradually becomes deeper in color with scaling and fissuring of the skin. This is the stage of dry epidermitis. With still larger doses of radiation, edema, vesiculation and superficial ulceration will occur, the stage of wet epidermitis. These reactions resolve slowly and require from several weeks to several months for healing, depending upon the extent of the injury and the degree of the
Fig. 199. Depigmentation of skin following deep radiation therapy, associated with atrophy and telangiectases.
reaction. Epilation which follows this type of reaction is permanent. An epilation persisting longer than six months is indicative of permanent epilation. If the radiation is more intense than the above, ulceration and necrosis will follow. The tissues pass through accelerated reactions described above or develop a dry necrosis, in either case eventually terminating in ulceration. Healing in this stage, if indolent ulceration does not follow, comes from the periphery and will take months before complete regeneration has occurred. The delayed, or chronic effects of radiation depend upon the dose delivered, the duration of the process, the quality of radiation, and the individual susceptibility. Telangiectases follow severe, but may follow mild, reactions, such as an erythema. They may appear in weeks or
Radiation Therapy in Dermatology
1273
months after exposure and are usually permanent. Atrophy is a common sequel to overexposure and is often accompanied by wrinkling and parchment-like changes in the skin. Occasionally deep scarring will develop due to changes in the underlying dermis. Other chronic changes are atrophy or'Pdestruction of the sebaceous and sweat glands, longitudinal ridging: fissuring or loss of the nails, and retardation of the nail growth. Verrucal forms of acanthosis, keratoses, and the formation of squamous and basal cell carcinoma or highly anaplastic carcinoma are known to develop as late sequelae (Fig. 200).
Fig. 200. Malignant changes in the skin of the hands following radiation therapy for a benign skin disorder many years previously. (Courtesy of Dr. Herbert Mescon.)
Tissue Response13 • 14. 16
There is much speculation as to the exact mechanism.of the effect of ionizing radiation on tissue. It seems probable that the action is not due to a single factor but to many factors. It is known that the irradiation of water will produce peroxides and that cells have a high water content. Hydration of cells favors radiation response, dehydration inhibits it. It is known that small amounts of peroxide are lethal to the enzyme systems of cells, particularly those containing the sulfhydryl radical (-SH). Cells contain certain large protein molecules which are vital to metabolism. It is possible that radiation by its direct effect on the key molecule can alter it so that it is incapable of performing its vital function. Oxygen deficiency, diminished blood supply and certain chemicals, e.g., cystein, tend to increase resistance to radiation. The practical application'.of this is immediately evident. Anemia, dehydration and dietary deficiencies should be corrected for the most favorable radiation response.
Edward N. Burke, George Levene
1274
PRINCIPLES OF TREATMENT
Radiation therapy properly given is considered an art as well as a science. The amount of radiation which is given is dependent upon the type of disease, the stage of the disease, and the patient's response to the radiation. For example, rosacea with telangiectases is not ordinarily treated by radiation. However, when this is accompanied by oily skin and acneform lesions, treatment is given to the point of clearing of the lesions. In years past the use of x-ray was empirical and occasionally indiscriminate. Today it is known that there are very few diseases which may be cured by radiation, but there are many diseases which may be helped by its proper use. If a skin disease fails to respond to conservative therapy or topical applications or general treatment, radiation therapy is prescribed if it is a responsive disease. Sufficient experience has accumulated to show that no permanent harmful effect to the skin from properly applied radiation occurs. Sulzberger, Baer and associates have shown in a large series followed for 28 years that no undesirable sequelae were present when 1000 r or less were used in factors commonly employed for benign skin conditions. I6 , 17 When 1000 to 2630 r were used, about 1.5 per cent of patients showed mild skin changes. There is no evidence that radiation given up to 1400 r, using techniques commonly employed, will produce undesirable skin changes. Treatments may be fractional, subfractional or intensive, depending upon the amount given, and they are given daily, twice weekly, weekly, or at longer intervals. Fractional treatment is the administration of small amount of x-ray, generally one-quarter of an erythema dose, at short intervals of time, usually weekly; the output is generally 75 r. Subfractional treatment is an exposure smaller than fractional. It is usually one-half of the fractional, 35 to 50 r. This is the type of treatment given to children or where treatment should proceed cautiously. Intensive treatment is wben one or more erythema doses are given in one sitting or over a short period of time. This is usually used in the treatment of malignancies of the skin. Generalized Dermatoses
The body is divided into areas to be treated. Typical areas are the head, arms, anterior body, posterior body, and legs. One area may be treated daily but the same field should not be treated more than once a week. The areas may be subdivided into smaller fields for ease of treatment and uniformity of dosage. The treatment area is carefully shielded by lead rubber sheeting for large areas, or lead foil for small areas. When large areas of the body are to be treated, it is important that the patient's
Radiation Therapy in Dermatology
1275
blood be checked before treatment and at intervals during the treatment. Anemia and leukopenia have been found to occur.IS Head. The head is divided into five areas, frontal, occipital, vertex, and two parietal areas, in a manner similar to that used for epilation which will be described later. The eyes, eyebrows and the face, if not involved, should be protected. Arms. The arms are treated by using three anterior and three posterior areas. The arm and forearm are divided equally into these areas. If the hands are involved they should be treated as separate areas, anteriorly and posteriorly. The fingers should be spread apart during treatment. The hand, as well as the arm should be treated separately. T~unk. The trunk is divided into four anterior and four posterior areas. Two of the areas are over the chest, and two are over the abdomen. Posteriorly, two areas should be over the scapulae, and two over the buttocks. Legs. Six areas are treated. Three areas, equally divided, are over the anterior surfaces of the legs and three over the posterior surfaces. The feet should be treated as separate areas, on the dorsal and plantar surfaces, and the toes should be held apart with cotton pled gets or cork. In treating the upper legs, the testes should be well protected. Each leg is treated separately. SPECIAL AREAS. Face. The eyes, eyebrows and hair are protected by suitable shielding. Three portals may be used, two lateral and one central. If there is little central involvement, only two lateral portals are necessary as there will be some central overlap. All other areas such as chest should be shielded with lead rubber. Axilla. The patient is placed on his side with the arm extended over the head. If the axilla is not a flat surface, the target skin distance may be increased to 30 cm., and a more homogeneous spread of the radiation will be obtained. It should not have to be mentioned that the therapy unit should be calibrated for this new distance if it is used. Gluteal Crease. The patient may lie either in the knee-chest position, assume the lithotomy position, or a prone position with the legs extended. The patient may be able to hold the natal crease apart, or strips of adheRive tape may be used to hold the buttocks apart. The spine should be protected, and the genitals should be well shielded.
Localized Patches
Localized patches of disease are treated after careful shielding of the normal surrounding skin. The protective shield may be made of lead rubber, lead foil, or other type of protective material having a lead equivalent sufficient for the kilovoltage of radiation used. When small lesions are treated, the lead foil may be cut to fit the lesion; the use of cork borers has been described to cut the lead, or it may be cut with a knife or scissors. Epilation. Several different techniques have been described for epilation. The Kienbock-Adamson technique is a safe and efficient method and has been used for many years with very satisfactory results. It is based on the principle of overlap radiation, and as a result there is some unequality of the dosage on the surface of the scalp. Strauss and Kligmanl9 have measured the amount of radiation that the scalp actually receives during an epilation. They have found that there are several
1276
Edward N. Burke, George Levene
areas on the scalp which receive a dosage of over twice the radiation administered at one treatment point. They state that the dosage which is necessary for permanent alopecia is greater than 1000 r. Total epilation of the scalp is to be preferred to the treatment of small focal areas of disease. To epilate a small area, it is carefully shielded with lead foil and 300 r unfiltered radiation is given at 100 kv. The Kienbock-Adamson technique20 consists in marking out 5 points on the scalp. These points are located approximately as follows: Point A is located 31 to 1 inch in front of the vertex. Point B is 31 to 1 inch inside the hairline over the frontal bone. Point C is located 1 to 2 inches inside the posterior hairline over the occipital bone. Points D and E are located 1 to 131 inches above and
c
Fig. 201. Diagramatic sketches to show the focal points in the Kienbock-Adamson technique. Left, Lateral view. Right, The relationship of the central portal to the lateral, anterior and posterior portals. slightly in front of the ears. The most important factor is to have the points between 431 to 531 inches apart. A most satisfactory method is by means of a knotted string, in which two knots are between 431 and 531 inches apart, depending on the size and shape of the skull. The points are then marked off on the closely clipped scalp so that the distance between points are equal (Fig. 201, A, B). Each point is treated with 300 r of unfiltered radiation at 20 cm. target-skin distance, using 100 kv. The tube is centered so that it is perpendicular to the planes of the other fields. The head should be supported with sand bags and the patient positioned for optimum exposure. In the treatment of uncooperative children, it has been necessary on occasion to use sedation, or when sedation alone has been unsuccessful, general anesthesia in the form of rectal Pentothal, or other general anesthestic. TREATMENT OF SPECIFIC DISEASES
Acne Vulgaris This disease is characterized by oiliness, comedone, pustules, papules and scarring. Radiation should not be used in the acute form or until
Radiation Therapy in Dermatology
1277
other adequate measures have been employed. It should be used in the chronic indurated type characterized by cystic changes or hypertrophic scars, and in the type with large comedones or accompanied by oily seborrhea. Sixty to 75 per cent cure of stubborn cases may be expected. 22 Treatment is 75 r unfiltered radiation given weekly to each area for six to eight weeks. Some recalcitrant cases will require a total amount of 1400 r given in fractionated treatments. In treating thick lesions, 1 to 2 mm. of aluminum should be used. Acne Varioliformis
A temporary response may be obtained in this condition. Topical remedies are of great value but they may be supplanted by small doses of radiation. The treatment is 75 r weekly of unfiltered radiation. Boils and Carbuncles
The development of antibiotics has made the treatment of boils and carbuncles by radiation obsolete. However, the pain associated with these conditions may be relieved by one dose of 250 to 300 r filtered with 1 to 3 mm. AJ.23 Dermatitis
Atopic. Atopic dermatitis in infants and very young children should not be treated by x-ray. The disease tends to be recurrent and care in treatment is advised. Treatment in older children and adults consists of subfractional treatments of 35 to 50 r unfiltered radiation at weekly intervals. Contact. Radiation has little effect on the acute stages of contact dermatitis,24 but it is helpful in relieving the itching. In the chronic lichenified type of dermatitis, 75 r unfiltered radiation weekly for four to six treatments will help. Infectious. X-ray should not be used in the acute stage but may be helpful in the chronic stage. Seventy-five r unfiltered radiation should be given weekly for six to eight treatments. Nummular. These are coinlike patches of eczema which itch and are associated with crusting and scarring. Seventy-five r of unfiltered radiation weekly will help. Crissey and Shelly25 have reported the beneficial results of x-ray in this condition in a controlled study. Seborrheic. Topical medication is preferred in this· condition. Occasionally when oiliness is excessive and there is considerable scaling, the condition may be helped by small doses of radiation. If t4ere is considerable erythema, subfractional doses of 35 to 50 r should be given at weekly intervals for six to eight weeks. The usual treatment is to give 75 r unfiltered radiati.on to the skin at weekly intervals for four to six treatments.
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Edward N. Burke, George Levene
Epidermophytosis
This condition responds well to fungicidal therapy. In the chronic eczematous or hypertrophic v2.rieties, several weekly fractionated treatments are helpful. Itching in the acute stage may be relieved. Treatment consists of 75 r weekly, unfiltered radiation for three or four treatments. Hem angiomas
The port-wine stain is not considered suitable for radiation therapy. Many of the hemangioma simplex, or strawberry marks, will spontaneously fibrose during the first year of life. There are other suitable methods of treatment such a~ sclerosing injections or the application of solid carbon dioxide. If a strawberry mark enlarges, or if it is located in a conspicuous area, treatment may be given by x-ray, contact therapy, or radium. X-rays may be used giving 200 to 250 r every six weeks, halting the treatment when the first sign of regression is noted, but not exceeding four treatments. It should be re-emphasized that treatment over the epiphyses, eyes and gonads should be avoided. Because of the ease of application, radium is well suited to the treatment of hemangiomas. A half-strength plaque of radium will produce an erythema of the skin if applied for 15 to 20 minutes. A dosage of less than an erythema, or ten minutes of treatment time, may be administered, using a half-strength plaque of appropriate size. The earlier in life the treatment is given, the more favorable the result. Usually two or three treatments at monthly intervals are required. Cavernous hemangiomas are best treated during childhood because of the fibrotic component which becomes apparent in young adult life. Two hundred to 250 r may be given by superficial x-ray at intervals of six weeks for a total of six to eight treatments. If the angioma is thick, appropriate filtration with aluminum should be used. Interstitial treatment with radium needles has been employed in this condition with excellent results. Radium plaques have also been used for this type of tumor. A double-strength plaque with 2 mm. of brass filtration may be used at 0.5 cm. If the lesion is thick, a distance of 1 cm. is recommended. A double strength plaque should be applied for 1%: hours. A half-strength plaque 2 by 2 cm. in size at the same distance requires seven hours. The dose may be repeated in three months if necessary. Hyperhidrosis, Bromhidrosis and Chromhidrosis
The technique in the treatment of these diseases is one which is designed to produce inhibition of the sweat glands. This is accomplished by giving suberythema doses of 225 to 250 r at intervals of three to four weeks with a filter of 1 mm. of aluminum. A total dose of 1400 r should never be exceeded. Dryness of the skin due to inhibition of the more sensitive sebaceous glands will occur.26 Only localized areas of hyperhidrosis should be treated. The generalized type is not suitable for treat-
Radiation Therapy in Dermatology
1279
ment, and the scalp and face should be excluded from treatment. The skin should be carefully watched during treatment and the production of erythema is to be avoided. Keloid
The chronic organized type of keloid will not respond to radiation. Young keloids less than 1 cm. in thickness will respond to suberythema treatments of 250 to 275 r at intervals of three to four weeks. Daily massage of the keloid is helpful and gives a sense of accomplishment to some patients or parents. Following surgical excision of keloids, a single dose of 300 to 400 r may be sufficient to prevent recurrence. Thick keloids should be treated with radium or by x-ray using filtration of 3 mm. of aluminum. The gamma rays of radium produce satisfactory results for the thicker lesions and the beta rays produce satisfactory results for the thinner lesions.. Lichen Planus
The acute and the subacute stages of the disease respond well to medical treatment, and fairly rapidly. When itching is associated with the acute stage it may be helped by the administration of 75 r weekly for four to six treatments. When the disease is generalized, the body is divided into five areas-head, trunk (two areas), arms and legs-and one area is treated daily with 75 r unfiltered radiation. The same area is not treated more than once a week, and the treatments are for a period of four to six weeks. NeuroderIllatitis
Radiation is helpful in relieving the itching associated with the skin reaction. The accompanying skin reaction is rarely helped. The symptoms during an acute exacerbation of the disease may be helped by small fractionated doses of x-ray. In the disseminated type it is necessary to treat the whole body. The technique for this has been previously described. The total dose should, again, never exceed 1400 r. Treatment is 75 r weekly for six treatments. It is inadvisable to treat infants or children. Psoriasis
Psoriasis will respond very well to several treatments of unfiltered radiation at weekly intervals. Radiation should not be used as a routine procedure as the disease is recurrent and the results are temporary. A careful history should be taken, particularly for prior radiation, before treatment is instituted. The subacute and chronic forms respond best. If the lesions reappear within three or four months, the treatment should not be repeated. Over-radiation should be carefully avoided. Treatment is 75 r weekly, unfiltered radiation for three to four weeks.
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Edward N. Burke, George Levene
Rosacea
Radiation is not indicated in the acute stage characterized by erythema and telangiectases. When accompanied by acneform changes, e.g., oily skin and pustules, x-ray given in weekly treatments of 75 r unfiltered radiation is of help. If the erythema is marked, subfractional doses should be used. Pruritus
The x-ray treatment of pruritus should not be continued for more than two or three visits. In many of our patients we have found that minute fissures or lacerations that could be seen only with a magnifying glass were the exciting cause of the itching, which disappeared very quickly with topical applications of bactericidal or healing ointments. The local treatment is accomplished by proper positioning, as previously described, and shielding of the spine and genitals. Fractionated treatments of 75 r unfiltered radiation for four to six treatments may be expected to produce good results in about half of the cases treated. Ringworlll of the Scalp
Radiation produces excellent results in tinea capitis and favus. Scarring due to disease, particularly in favus, becomes evident following treatment, and parents should be advised that the disease and not the irradiation produces this. In treating favus, the output should be increased to 350 r. The ears and face should be protected during treatment. Kligman21 has shown that in the pathogenesis of tinea capitis due to M. audouini, the infection passes through various stages. These stages are an incubation period, a period of enlargement and spread, a refractory period and a period of involution. The refractory state is a stage which develops after three to four months. It is of importance in that following epilation at this stage, reinfection will not occur, and subsequent treatment with fungicides is not necessary. For this reason it seems logical that for the first three or four months fungicides applied locally should be employed. After the development of the refractory period, epilation may be used. Kligman, in addition, points out that the oft reported frustrating failures of local epilation are due to treatment in the earlier stages before the development of refraction. Local epilation in selected cases is possible during this refractory stage. Defluvium begins in three weeks and regeneration is complete at four months. When hair begins to fall, it may be removed by using adhesive tape, or by manual removal. It is needless to state that the patient should wear a stocking cap at this time to prevent dissemination of infection. Tinea Barbae
',Tinea barbae may be cured by epilation of the beard. This, however, is a most serious procedure and permanent skin damage often follows;
Radiation Therapy in Dermatology
1281
it is not a recommended procedure. Fractionated treatments of 75 r daily for a total of 400 r will often be of benefit. Erythema is to be avoided. Warts Plantar warts may be removed by the application of a single large dose of 1500 r unfiltered radiation. The best results are obtained when the wart is of the thick hyperkeratotic variety and at least part of the thick cornification is removed prior to treatment. The lesion should be carefully shielded and the treatment should not be repeated. Occasionally a filter of 1 mm. of aluminum should be used when the wart is thick and sclerotic. Verruca vulgaris is best treated by other means. It may be treated with a single intensive treatment of 1500 r. The treatment should not be repeated. Malignancies of the Skin
: An accurate evaluation of the tumor size and allowance of an adequate margin, and treatment with sufficient radiation with due consideration for healing, are basic tenets. The size of the lesion, the rate of treatment, and the total amount of radiation should be outlined before the onset of treatment. Widmann, of Philadelphia, treats basal cell and squamous cell carcinomas in the same manner, without regard for sensitivity.27 This is an excellent method, for some basal cell carcinomas are sensitive and others quite resistant, and some squamous cell carcinomas respond in the same manner. Holmes and Schulz divide lesions of the skin into small, moderate and very large lesions. 28 Small lesions of the skin, less than] cm. in size, are treated by 100 kv. x-ray. They may be treated with a single massive dose of 2400 to 3000 r, or treatment may be divided, giving 1200 I' on three successive days. If the lesions are small and shallow, 1000 I' every other day for three treatments is sufficient. If the lesions are thick, i.e., having an elevation of 5 mm. or more, 1500 I' every other day for three doses should be given. Moderate lesions having a size of 1.5 to 5 cm. are treated by 500 I' daily for a total of 3500 to 5000 1', depending upon the size and thickness of the lesion. Thick lesions should be filtered with from 1 to 3 mm. of aluminum. Large lesions greater than 5 cm. in size may be treated with 140 kv. or 200 kv. The rate of administration may be from 200 to 500 r daily. The treatment must be carefully administered due to the large treatment area, and the likelihood of poor healing or necrosis. When using 200 kv., it should be remembered that a sizeable dose is produced in the normal tissue lying at a considerable depth beneath the tumor. Damage to the brain has been reported following the treatment of basal cell carcinoma in the overlying skin. 29 The first course of therapy should be adequate so that further radiation is unnecessary. If, on follow-up several weeks after completion of treatment, an additional 1000 I' is deemed necessary, it may be given to the local area of suspicion. 27
Skin malignancies overlying cartilage of the nose or ear are best treated by surgery. Radiation by superficial x-ray in these regions may
1282
Edward N. Burke, George Levene
lead to occasional painful chondritis. In lesions about the eye, the eyelid should be most carefully shielded to avoid the production of radiation cataract or other injury. Contact therapy is of value in treating lesions about the eye, overlying cartilage, or in the region of the gonads or epiphyses. Pendergrass and Chamberlain 6 recommend contact therapy dosages of from 5000 to 10,000 r, with a mean dose of 7000 r. They use as a rule of thumb an adjustment of penetration so that "dY2" (where dY2 is equal to the half value of the surface dose) coincides with the deepest portion of the tumor plus a slight margin of safety. Radium is of great value in the treatment of uncooperative patients or as an alternative method of therapy. Because of the ease of administration and the excellent results with x-ray, however, radium has been largely supplanted. Flat or shallow lesions are treated with radium at a distance of 0.5 cm. Elevated lesions are treated at a distance of 1 cm. Filtration with 2 mm. of brass, 2 mm. of silver, or 0.5 mm. of platinum is used. Lesions less than 2 cm. in size may be treated with massive doses-6 to 8 T.E.D. (threshold erythema dose), or 6000 to 8000 gamma roentgens. Large lesions should be fractionated by giving 1000 gamma r daily, or every other day, for a total of 6000 to 8000 gamma roentgens. The use of Quimby's or Patterson and Parker's charts enables the conversion of milligram-hours of radium into gamma roentgens. CONTRAINDICATIONS
The contraindications to radiation therapy may be absolute or relative. 30 The absolute contraindications may be those relating to the patient, apparatus or operator. Blood dyscrasias, previous radiation up to skin tolerance, skin diseases which are characterized by atrophy, or which result in atrophy, disease with scarring, or when acute inflammation is present, are absolute contraindications. The use of technicians without training, or poorly trained, should not be permitted. It should not be necessary to state that a physician should set up each patient, check the filter and the other factors to be used before treatment is begun. The use of apparatus which has not been calibrated is not permitted. Failure of a condition to respond after a fair trial is an indication for terminating therapy. Relative contraindications are those in which there is a temporary impediment to treatment. They may be due to anemia, dehydration, poor nutrition, general debility or inability to cooperate. The use of strong agents such as the heavy metals, iodine, mercurochrome, mercury, sulfur, coal tar and iodoform should be avoided before, during and after radiation therapy. These agents tend to sensitize the skin to the effect of radiation and an accelerated, severe reaction will be produced. The use of any agent on the skin following radiation, except extremely bland ointments, is to be condemned. Physical agents such as ultraviolet and infra-red rays, heating pads, or exposure to sunlight will intensify radiation reaction. In addition, there are certain individuals who are extremely
Radiation Therapy in Dermatology
1283
sensitive to the action of radiation. They are usually persons of fair complexion who have a history of extreme sensitivity to the sun. Accurate and complete records should be maintained for protection of the patient at all times. Table I SUMMARY OF X-RAY TREATMENT OF SKIN DISEASES DISEASE
Acne vulgaris Acne varioliformis Boils and carbuncles Atopic dermatitis Contact dermatitis
Infectious eczematoid dermatitis Nummular dermatitis
Seborrheic dermatitis Epidermophytosis
TREATMENT
Fractionate, 75 r weekly Several doses, fractionate, If scalp infected, 38 r weekly by Adamson-Kiento clearing bock technique 250 to 300 r, filtered with 3 AI, 1 treatment Subfractionate. 35 to 50 r weekly 75 r, 4 to 8 treatments
75 r, 4 to 6 treatments Fractionate, 75 r weekly, 6 to 8 weeks 75 r weekly, 4 to 6 treatmenta
Fractionate, 75 r weekly. 3 or 4 treatments
Hyperhidrosis, bromhi- Fractionate, 75 r weekly drosis, chromhidrosis 225 to 275 revery 3 to 4 Keloid week"_ filtration 3 Al for thick lesions Lichen planus Hypertrophic type Neurodermatitis
PsoriasiB
ALTERNATIVE
35 to 50 r weekly, for 6 to 8 treatments. if erythema is marked
200 to 225 r filtered, monthly
COMMENT
Topical remedies are of greatest value. Will relieve pain.
Chronic types of dermatitis. Pruritus of acute stage may be helped. For use in chronic stage.
If 4 to 6 treatments do not help, do not persist. (Acute vesicular type respon:is best.) Generally not satisfactory Give up to 1500 r if necessary. Stop when blanching occurs.
75 r fractionate, 4 to 6 treatments 75 r filtered with 1 AI, up to 1400 r if necessary 75 r weekly, 6 treatments 75 r weekly
For relief of pruritus. Generally inadvisable to treat rapidly reClIrring types or
Rosacea
Pruritus Ringworm of the scalp Favus Tinea capi tis Tinea barbae Warts
75 r, fractionate, for total of 600 r 75 r, fraction ate, 4 to 6 treatruents Epilation Epilation 75 r every other day to 400 r. l'rythema is avoided 1500 r at OIle sitting; if thick filter with 1 mm. Al
38 r, fractionate, if erytherna is present
Occasional spot epilation, generally unsatisfactory Occasionally 250 r
acute stage. For pustular and oily stages.
To be used only in severe cases. Do not repeat.
REFERENCES 1. Pfahler, G. E.: Development of Roentgen Therapy During Fifty Years. Radiology 45: 503-521, 1945. ~!. Pusey, W. A.: The History of Dermatology. Springfield, Ill., C. C Thomas, 1933. 3. Glasser, Otto: Wilhelm Conrad Roentgen. Springfield, Ill., C. C Thomas, 1934.
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4. Cipolhro, A. C. allll MutsdlUlIer, A.: Absorption of Roentgen Rays by the Skin. Arch. Dermat. & Syph. 41: 87-97, 1940. 5. Cipollaro, A. C.: Beryllium Window Radiations for Superficial Therapy. Arch. Dermat. & Syph. 62: 214-221, 1950. 6. Pcndergrass, E. P. and Chamberlain, R. H.: In Clinical Therapeutic Radiology, U. V. Portman, Editor. New York, Thomas Nelson & Sons, 1950. 7. Glasser, 0., Quimby, E. H., Taylor, L. S. and Weatherwax, J. L.: Physical Foundations of Radiology. New York, Paul B. Hoeber & Sons, 1947. 8. Desjardins, A. U.: Radiosensitiveness of Cells and Tissues. Arch. Surg. 25: 926, 1932. 9. Akerman, L. V.: Cancer-Diagnosis, Treatment and Prognosis. St. Louis, C. V. Mosby Co., 1954. 10. Alien, A. C.: The Skin. St. Louis, C. V. Mosby Co., 1954. 11. McKee, G. M., and Cipollaro, A. C.: X-rays and Radium in the Treatment of Diseases of the Skin. Philadelphia, Lea & Fcbiger, 1946. 12. Liebow, A. A.: Effects Produced on Hair by Atomic Bombs. Ann. New York Aead. Sc. 53: 688-689, 1951. 13. Jung, F. T.: Physiological and Chemical Changes in Radiation Injuries. Arch. Dermat. & Syph. 64: 5.55-561, 1951. 14. Lea, D. E.: Actions of Radiations on Living Cells. New York, The Macmillan Co., 1947. 1.5. Patt, H. M.: Protective Mechanisms in Ionizing Radiation Injury. Physiol. Review 33: 35-76, 1954. 16. Sulzberger, M., Baer, R. and Borota, A.: Do Roentgen Ray Treatments as Given by Skin Specialists Produce Cancer or Other Sequelae? Arch. Dermat. & Syph. 65: 639-655, 1952. 17. Baer, R. L., Borota, A. and Sulzberger, M.: The Late Therapeutic Results Produced by Low Voltage Roentgen Rays and Other Forms of Therapy in Certain Benign Chronic Skin Diseases. J. Invest. Dermat. 19: 325-331,1952. 18. Poscher, F. and Kanee, B.: Reactions of the lIematopoetic System of Agents Used in the Treatment of Dermatoses. Arch. Dermat. & Syph. 53: 1-5, 1946. 19. Strauss, J. S. and Kligman, A. M.: Distribution of Skin Doses over Scalp in Therapy of Tinea Capitis with Superficial X-rays. Arch. Dermal,. & Syph. 69: 331-341, 1949. 20. Adamson, H. B.: A Simplified Method of X-ray Application for the Cure of Ringworm of the Scalp: Kienbock's Method. Lancet 1: 1378, 1909. 21. Kligman, A. M.: The Pathogenesis of Tinea Capitis due to Microsporon Audouini and Microsporon Canis. J. Invest. Dermat. 18: 231-246, 1952. 22. Crawford, G. M., Luis:;trt, R. H. Jr., and Tilley, R. F.: Roentgen Therapy in Acne. New England J. Med. 245: 726-728, 1951. 23. O'Brien, F. W.: The Treatment of Severe Carbuncles by X-ray. New England J. Med. 220: 917-919, 1939. 24. Kemp, T. S., and Kligman, A. M.: Effect of X-rayon Experimentally Produced Acute Contact Dermatitis. J. Invest. Dermat. 23: 423-425, 1954. 25. Crissey, J. T., and Shelley, W. B.: A Controlled Study of the Effect of X-ray Therapy in Certain Nonmalignant Dermatoses. New England J. Med. 247: 965-970, 1952. 26. Borak, J. (translated by E. T. Teddy): The Radiation Biology of the Cutaneous Glands. Radiology 27: 651-655, 1936. 27. Widmann, B. P.: Clinical Therapeutic Radiology; U. V. Portman, Editor. New York, Thomas Nelson & Sons, 1950. 28. Holmes, G. W. and Schulz, M. D.: Therapeutic Radiology. Philadelphia, Lea & Febiger, 1950. 29. Duggan, G. S., Stratford, J. G. and Bouchard, J.: Necrosis of the Brain Following Roentgen Irradiation. Am. J. Roent. & Rad. Ther. 72: 953-960, 1954. 30. Lane, C. G.: Roentgen Rays ill Treatment of Cutaneous Disease. Arch. Dermat. & Syph. 61: 426, 1950. 750 Harrison Avenue Boston 15, Massachusetts