This article is from the 1911 Encyclopaedia Britannica. Medical science has made many leaps forward since it has been written. This is not a site for medical advice, when you need information on a medical condition, consult a professional instead.
"RADIOTHERAPY. - Since 1910 there have been notable developments, extending the practice of X-ray treatment (see 28.887) into the wider field now included in radiotherapy, a term which had not then come into general use. Strictly speaking, under this term should be included treatment by all kinds of rays; thus treatment by heat, by sun's rays, by ultra-violet rays, by X-rays and by the rays of radio-active substances, all come under the etymological term of radiotherapy. In practice, however, it is restricted to the application of ultraviolet rays, X-rays and radium rays. Amongst radiologists, the term has undergone an even sharper definition, so that radiotherapy is applied by them to treatment with X-rays alone, the terms radiumtherapy (or, in France curietherapy, in honour of the discoverer of radium) being applied to treatment with the rays of radium and other radio-active substances. Treatment by means of high frequency currents and diathermy are included rather under the term electrotherapy.
Ultra-violet Rays. - These rays to a large extent are the essential feature of those forms of medical treatment which depend upon exposure to sunlight (heliotherapy). Probably this is not the whole story. Even though heat rays may also play some part, experience of the treatment of wounds by sunlight in France during the World War indicated that a degree of benefit arises from exposure to sunlight which cannot be entirely attributable to warmth and ultra-violet rays. On the other hand, in the Finsen light treatment of lupus and in the treatment of tuberculosis at high altitudes, ultra-violet rays probably play a predominant part. It is uncertain how these rays act; they penetrate but a fraction of a millimetre into the epithelium and yet the fact that in tropical countries where sunlight is great, the white races show a proverbial irritability which does not characterize the pigmented native races, suggests that in the one, effects are produced by the ultra-violet rays which the pigment of the other is able to eliminate. Certain it is that under ultra-violet light, persons vary in the appearances they present, those who freckle or tan easily when exposed to sunlight showing the potential freckles or bronzing of their skin by dark marks which are absent from the skins of those who do not freckle or tan easily. In this connexion, it is noteworthy that those tuberculous persons are said to derive greater benefit from a sojourn at high altitudes who normally tan easily under sunlight, than those who do not. The rays are bactericidal, but whether part of their action lies in this direction, is unknown.
X-rays. - The X-rays which were discovered by Röntgen in 1895 are employed in medicine in two ways, firstly, as an aid to diagnosis when they form those branches of the subject known as radioscopy and radiography, and secondly, for the actual treatment of conditions when diagnosed. Thus by means of radioscopic or radiographic examination it may be found that there is a tumour in the chest, and as a result of that diagnosis it may be decided to institute treatment (radiotherapy) by means of X-rays or radium rays or the two combined.
X-radiation has the advantage that considerable doses can be employed. It has the disadvantage that the X-rays are frequently not of sufficiently penetrating power to serve for the treatment of tumours deep within the body. Three varieties of X-rays are used, the difference consisting in variations in wave lengths and in penetrating power. These varieties are known clinically as " soft," " medium " and " hard " X-rays, the soft rays being those of longer wave length and less penetrating power, and the hard rays being those of shorter wave length and greater penetrating power. The softest X-rays are not used clinically; those employed in the treatment of ringworm for example are " medium soft " since it is necessary for penetration to reach as deeply as the hair follicles. Medium hard and hard X-rays are used where a layer or mass of tissue some little distance beneath the surface is to be treated.
For the better treatment of new growths removed some distance from the surface of the body, there is a tendency at the present time (1921) to increase the hardness of the rays to the utmost extent with the object of producing a radiation that approximates in some degree to the gamma rays of radium in penetrating power. Chief amongst the new growths that are the subject of this " deep therapy " with intensely penetrating X-rays are uterine fibroids. The production of soft to medium X-rays requires an apparatus capable of generating about ioo,000 volts, for deep therapy a voltage of about 200,000 is necessary and the aim of radiologists is to get a still higher voltage. The method employed is essentially use of a series of transformers.
It is unnecessary here to enter into a detailed examination of the methods whereby X-ray dosage is determined, but it is obvious that estimation of the dose is one of the most important points in connexion with radiotherapy. In the case of radium, the matter is relatively simple, for the output of rays from the radium is constant, but in the case of the X-ray bulb, quite apart from variations in the primary current, the conditions of the bulb vary within wide limits, and the output of the bulb in X-rays varies accordingly. An important advance has been made in recent years by the introduction of the Coolidge tube in which by means of a different working principle the output of X-rays can be kept fairly steady. Under all circumstances, the output of an X-ray bulb is heterogeneous, the bundle of rays emitted is partly penetrating, partly soft, and in order to produce a more or less homogeneous bundle of rays for purposes of treatment, it is necessary to eliminate the softer varieties by means of filters. These filters are of different kinds but the chief are aluminium, zinc, copper and lead. For absorption of the specific secondary radiations produced when gamma or X-rays impinge upon metals, such substances as rubber, gauze, cardboard are used.
When a more or less homogeneous beam has been produced, it is necessary to calculate the dose employed in any given case for comparison with other cases. Various means have been adopted to this end, of which the commonest is the Sabouraud's pastille which consists of barium platinum cyanide and changes colour from green to yellow under a certain dosage of the rays. It was thought at first that this colorimetric test would be generally applicable, but it was soon found that the change is not brought out by X-rays of all degrees of penetration and is fallacious as a guide to gamma radiation of radium. It is now largely employed as a test of dosage during the X-ray treatment of ringworm and other skin diseases, but it is recognized that it must only be employed with caution, with rays of medium hardness, and for superficial conditions. Another form of test is electrical (ionto quantimeter) in which the rate of discharge of a charged gold leaf forms a measure of the output of X-rays. Another method depends upon the chemical reduction of iodine from iodoform in a chloroform solution and is probably the most scientifically accurate of all the methods which have been devised. Yet other methods depend upon the correlation between the effects produced by X-rays on the one hand and the gamma rays of radium on the other. Here the production of identical degrees of fluorescence on the fluorescent screen or of silver deposit on the photographic plate or of biological effects on the animal cell has been aimed at in standardization.
So far as treatment is concerned, it is obvious that a biological test is the most satisfactory. The one commonly used is known as the " erythema dose," meaning thereby that dose of X-rays which leads to a reddening of the skin a few days of ter application and subsequently to slight bronzing, without blistering or other damage. On the other hand there is no doubt that the various cells of the body do not react to radiations in the same degree and partly on this account and partly because of the operation of the law of inverse squares, it is obvious that the skin over a tissue being irradiated may itself receive an injurious dose while the tissue in question is receiving the correct dose. Hence when a tissue some distance beneath the surface is under treatment it becomes necessary to irradiate it through different portals, so that each area of skin shall receive less than the erythema dose, although the tissue in question gets the full amount that the radiologist wishes to give it; this method of cross fire is largely employed.
Treatment by means of radioactive substances largely resolves itself into treatment by means of the beta and the gamma rays of radium or occasionally mesothorium. Just as X-rays vary in degree of penetration, so do the rays of radium. The so-called alpha rays are little penetrating, being stopped by about 32cm. of air. The beta rays, which are particulate negative electrons, are more penetrating but their penetrating power varies over a wide field, some of the softest being as easily absorbed as alpha rays, some of the hardest approximating to the soft gamma rays in penetrating power. Gamma rays are aether vibrations and they, too, vary in degree of penetrating power. Their wave length is the shortest of any form of vibration known, and the most penetrating gamma rays can be detected through several inches of lead.
The alpha rays are but little used, the only methods of employment being in the way of radium emanation dissolved in saline solution, or of needles upon which " active deposit " from radium emanation has been collected. In either case the emanation water or the active deposit needles must be introduced into the system - whether intravenously or into the solid tissues - otherwise the alpha rays would have no power to act. In either case, too, they act along with the beta and gamma rays produced by the active deposit.
Beta radiation is always used in conjunction with gamma radiation, but inasmuch as the ionizing power of the beta ray is about so times as great as that of the gamma ray, it follows that when beta radiation is being employed, the gamma radiation may probably be ignored. Beta radiation is used for merely superficial conditions and the radium salt which supplies it is spread over a flat or curved applicator and is covered with a thin layer of varnish, mica or aluminium or is placed in a thin glass tube; the beta rays which traverse thin solid filters act. upon the tissue in the neighbourhood of which the radium is placed. Instead of a radium salt one of its products, viz. radium emanation is often employed clinically. No essential difference is introduced by the use of this emanation excepting that its intensity undergoes a progressive diminution with time since it falls to half value in 3.85 days. Early rodent cancer, certain conditions of the eyelids, some cutaneous non-malignant tumours and birth-marks, are treated successfully in this way.
Gamma radiations are used where deep penetration is required, but the law of inverse squares approximately holds good in their case also, a matter of fundamental importance in treatment. The substances used as filters when radio-active materials are employed in treatment are not quite the same as those used along with X-rays. Since one of the main objects in employing radium is to utilize the highly penetrating gamma rays, the filters employed are generally of the higher atomic weights, silver, brass, gold, lead, platinum, and there is some reason for believing that the more highly penetrating the rays, (i.e. the denser the filter through which they have passed) the less is undesirable damage suffered by the tissues.
The method by which X-rays and radium rays produce their effects are not thoroughly understood, but it is certain that dosage must vary according to the type of cell which it is desired to influence. Thus the vulnerability of skin is not-the same in different individuals nor even in different regions in the same individual; the vulnerability of the squamous cell is not the same as that of the columnar cell; the vulnerability of renal cells differs in the convoluted tubules and in the conducting tubules. Even in the fur of animals it is possible to recognize a differentiation, for a certain amount of X-radiation will lead to a destruction of the pigment forming cells in the hair of a black rat, while a little more radiation will affect the cells themselves. In the former case there is no epilation but the hair comes white instead of black, in the latter the hair falls out and baldness results.
If the question be carried still further back and the behaviour of the cells themselves under radiation be considered, it has been found that the rays may act principally, though not exclusively, upon the nucleus or upon the cytoplasm or upon the cell membrane or upon any paraplastic material within the cell. The greater amount of work in this direction has been carried out with radium but there is little doubt that the effects of X-rays are similar. In part, changes are produced owing to the fact that the radiations break down complex chemical substances into simpler constituents. In this way, the osmotic tension of the cell or nucleus affected is raised and a dropsical condition results which can often be recognized microscopically. Other forms of degenerative change produced are fatty and mucoid. Thus radiation, if in great doses, will lead to fatty change in voluntary muscle of man and most animals or in renal cells of the cat. Under large doses of radium, mucoid changes are excessively common in all parts which normally produce mucus, but in addition, there is a great tendency for cells which ordinarily do not form mucus to undergo mucoid degeneration. Sometimes the cytoplasm of the cells disappears, though not obviously by way of either of these changes, with the result that the nucleus lies naked in the middle of the cell and separated from the cell membrane by a considerable distance. So far as the nucleus is concerned, changes produced by radiations may be intense. In cells such as those of testicle or intestine which are often found in mitotic division, mitosis is arrested or abolished. In other nuclei there may be evidence of vacuolation or the nucleus may be converted into a mere empty sac, or the nuclear membrane may disappear, or the entire nucleus may be represented by a few points of stained material or, finally, the nucleus may disappear altogether.
Thus in one or other way, changes are produced as the result of irradiation in the tissues upon which those rays impinge and the effects produced will depend upon (I) the type of cells affected, (2) the quantity of rays employed, (3) the length of time those rays have acted.
It must be remembered that the biological cell usually acts in one or other of two opposite directions when exposed to a physical agent according to the intensity with which the agent acts. Thus we distinguish between a stimulating or beneficial effect and an irritative or injurious effect. There is reason to believe that both of these may follow upon irradiation. In the case of malignant new growths, there is no doubt that death and destruction of the neoplastic cells occur where the rays act in all their intensity, but there is equally no doubt that because of the law of inverse squares and the specific absorption by the tissues a point is reached at which the injurious effect on the malignant cells which we desire passes into a stimulant effect which we may have reason to deplore. If this stimulus act on young and actively growing malignant cells at the periphery of the growth our irradiation will do more harm than good to the patient. There can be little doubt that in the early clays of radiotherapy, some cases of malignant disease ran a more rapid course as the result of the irradiation treatment than otherwise they would have done. For this reason, the essential point of their treatment by means of radium consists in an endeavour to deal with the peripheral neoplastic cells.
On the other hand, changes may be produced in cells which we are unable to recognize microscopically. Recently the treatment of exophthalmic goitre has been largely and for the most part, successfully, carried out by irradiation and yet if the thyroid body be examined from animals exposed for many hours to the gamma radiations of radium bromide, it may be doubtful whether histological changes can be detected. Similarly, intense gamma radiation of the male frog produces no testicular changes that can be detected with certainty, and yet far less radiation produces marked changes in the tadpoles derived from normal ova fertilized by such radiated spermatozoa.
It follows from what has been said above, that radiotherapy is not without its special dangers. Amongst the disadvantages to which the irradiations may give rise, too extensive destruction of tissue on the one hand or stimulation of new growth on XXXII.-8 the other are relatively obvious but the dangers are more insidious. Recent work has shown that long continued exposure to minute doses of radiation (in addition to the well-known occasional production of skin cancer) leads to blood changes which in course of time become a pronounced menace to life. Not only are red and white blood cells destroyed, but the rays appear to exert a deleterious effect upon the blood-forming tissues with the result that an aplastic arnemia becomes established. Obviously, the protection of the personnel in hospitals and similar institutions where X-rays and radium are used becomes a matter of great importance.
It is probable that X-rays and radium will always continue to be employed side by side owing to the special advantage which each form of radiation possesses, and in some cases it is certain that the best results are obtained in combination.
It will have appeared from what has been said above that radiotherapy is largely - though by no means exclusively - concerned with the treatment of new growths. Irradiation by one or other method is used in cases of uterine fibroid and in cases of inoperable cancer, sometimes with astonishingly good results. It is also used in conjunction with operation for cancer with the object of warding off recurrences. Sometimes cancers, inoperable when they first come under observation, are rendered operable by treatment with radium. And, frequently, when surgery has done all that is possible a considerable degree of relief is given by irradiation.
In addition to their use in the treatment of new growths, X-rays and radium have been tried in most of the chronic forms of disease. When surgery or medicine fails to relieve a case, it is usual to try irradiation. Sometimes the results are surprisingly beneficial, but the limits of utility of the rays still need to be determined. (W. S. L-B.)
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