Radiotherapy (Contents)

RADIOTHERAPY. Contents: Biological action of X-rays ........634 Distribution and absorption of X-ray energy ...;...................638 Quantimetry .................... 640 Qualimetry........,............642 Methodology R......................644 Damage caused by X-ray rays . . .645 R. in dermatology..................64 8 R. in gynecology..........'........6 50 R. in surgical diseases..........653 R. in internal diseases............658 Radiotherapy, the application of X-ray rays for therapeutic purposes. Soon after the discovery of X-ray rays, it was found that these rays could exert biological action on animal tissues: as a result of the application of X-ray rays for diagnostic purposes, reddening of the skin, loss of hair, and in some cases even ulcers sometimes occurred on the irradiated areas. These observations led to attempts to apply X-ray rays for therapeutic purposes. As early as 1896, Freund made an attempt to influence naevus pigmentosus pilosus by means of irradiation with X-ray rays. This marked the beginning of the treatment of skin diseases with R. (superficial radiotherapy). In the following years, this method was tried in almost all skin diseases and took a firm position in this field of medicine. Until about 1903, only the action of X-ray rays on the skin was known. By this time, Albers Schonberg had published his research on the action of X-ray rays on the sex glands in males. Following this, reports appeared by Heinecke on the destructive action of X-ray rays on the white elements of blood, and works by Halberstadter and others on the influence of X-ray rays on the sex glands in females. These studies laid the foundations for so-called deep R., which aims to influence organs and tissues located deep in the human body by means of X-ray rays, and which in recent decades has developed into a powerful discipline with its own methodology, based on numerous clinical observations and experimental research. Biological action of X-ray rays. The biological action of X-ray rays is the result of the absorption of X-ray energy by cells. Our knowledge of the essence and details of both the stages of transformation of X-ray energy and the physicochemical processes occurring in the cells during this is extremely meager due to the extreme complexity of biological phenomena. Only the so-called photoelectric effect is certain, which is common to all types of electromagnetic radiation and consists in the detachment of electrons from the atoms of the cell. Due to the relatively short wavelength of X-ray rays and the significant magnitude of their inherent quantum, these electrons possess considerable energy, which explains the particularly powerful biological action of X-ray rays. Regarding the further stages of processes occurring in cells under the influence of X-ray rays, our knowledge does not go beyond more or less reliable hypotheses - changes (denaturation) of cellular proteins, increase in temperature, possible accumulation of high temperatures in certain focal points (Dessauer's Punktwarmenhypothe-se), changes in cellular enzymes, etc. The final results of these processes in the form of morphological changes, and partly also functional changes, that are subject to histological research, are much better studied. These changes mainly concern the cell nucleus. Swelling and vacuolization of the nucleus (vacuolar degeneration) are noted, and later its pyknosis. Chromosomes are particularly sensitive to X-ray rays. In this connection, the function of reproduction is primarily affected. Depending on the degree of exposure, cell division is delayed or completely stopped, which is expressed in a significant decrease or absence of mitoses in the irradiated area. Most authors adhere to the view that these changes in the cell nucleus are the most essential and characteristic of the biological action of X-ray rays (Kernhypothese). According to these authors, changes in the protoplasm occur later, when the cell is already dying, i.e., they have a secondary character. There are supporters of the primacy of changes in the protoplasm under the influence of X-ray rays (Protoplasmahypothese; Weil and Frenkel, Niirenberger). The same applies to the question of changes in the cell membrane in the sense of increased permeability of the cell membrane under the influence of X-ray rays. From the area of the influence of X-ray rays on the cell (plants, unicellular organisms), the question of the possibility of influencing bacteria by means of X-ray rays is of particular interest. Numerous experimental studies have established that X-ray rays have a bactericidal effect on bacteria in vitro, but such enormous doses are required that the possibility of practical application in a living organism is completely excluded. The undoubted influence of X-ray rays on bacterial processes (tuberculosis, acute inflammatory processes) is based on the formation of protective enzymes, stimulation of connective tissue, etc. Undoubtedly, in addition to the above-mentioned morphological changes in the organism under the influence of X-ray rays, significant functional changes occur, manifested in changes in the basic and intermediate metabolism, in the influence on the autonomic nervous system (lowering of blood pressure) and the functions of the endocrine glands. Probably, there is hardly a function in the body that would remain completely unaffected by the action of X-ray rays. But all these questions are still in the study stage. In connection with this multifaceted influence of X-ray rays on various systems and organs of the human body, the general disorders observed in humans after irradiation with relatively large doses stand out (Röntgenkater of German authors). They consist in symptoms of general malaise, headache, nausea, vomiting, occasionally accompanied by slight increases in temperature. These phenomena appear several hours after irradiation and disappear after 1-2 days. In general, the intensity of these phenomena increases with the size of the X-ray dose given to the patient and stands in a certain dependence on the irradiated area of the body. The most frequent and relatively sharply expressed general reactions occur after irradiation of the abdominal area. Numerous hypotheses have been expressed about the causes of these phenomena: poisoning by ozone and harmful nitrous gases formed due to high voltages at the poles of the X-ray tube, inductive charging of the patient's body, and much else. The assumption that the cause of these general phenomena lies in the depletion of blood and tissue fluids of sodium chloride (Volz, Holzknecht, Sielmann) rests on more solid grounds. The favorable effect of the introduction of an isotonic solution of table salt on the phenomena of Röntgenkater serves as partial confirmation of this assumption. Most likely, these phenomena are the result of poisoning of the body by products of cell decay (necrohormones) under the influence of X-ray rays. Connected with this protein decay is probably the above-mentioned depletion of tissues of NaCl. The biological action of X-ray rays is characterized by certain features that are of great importance in their application in radiotherapeutic practice. Since the biological effect is the result of the absorption of X-ray energy by tissues, the degree of this effect, all other conditions being equal, depends on the magnitude of the so-called dose, i.e., the amount of X-ray energy absorbed by the tissue. The higher the X-ray dose delivered to the cell, the greater the changes obtained in it as a result of irradiation. From the degree and depth of these changes, and the structure and vital activity of the cell, depends the possibility of restoring the disturbed function and returning the cell to normal life. As a result of the action of large doses, all disturbances can reach such a high degree that the restoration of normal vital activity becomes impossible and the cell dies. Until now, the question of the so-called "irritating action" of X-ray rays is still debated in the literature. By "irritating" action is meant such an effect as a result of which there is an increase in the vital activity of the cell, an increase in its specific function, and possibly also the function of reproduction. (Instead of the inaccurate term "irritating action," it is more correct to speak of a stimulating biopositive action in contrast to the inhibiting bionegative effect.) The teaching of the "irritating action" of X-ray rays is based on the so-called Arndt-Schulz law (see Arndt-Schulz law). By analogy, some radiologists began to explain certain phenomena observed with the application of small doses of X-ray rays by the biopositive, stimulating effect of these small doses. As an example, one can mention the increase in blood clotting under the influence of irradiation of the spleen with small doses of X-ray rays, etc. For some time, the assertion played a special role that small doses of X-ray rays can cause accelerated growth of malignant tumors.

Not to mention that according to the latest research, the aforementioned position of Arndt-Schulz does not have the character of a general biological law, it has been established that in those cases where indeed a biopositive effect _g was obtained under the influence of irradiation with small doses of X-rays, the latter is explained not by the direct stimulating effect of X-rays, but by the action of decay products, i.e., ultimately as a result of the depressing bionegative effect of X-rays. The controversy over the possibility of a biopositive effect of X-rays has not yet been finally resolved, but most authors are inclined to recognize exclusively the destructive bionegative effect of X-rays (see Radiotherapy).

A peculiar feature of the biological action of X-rays is the circumstance that the effect of the impact does not manifest immediately, but only after the passage of some time. Between the moment of irradiation and the manifestation of the reaction, there is a so-called latent period, the duration of which depends to a significant degree on the magnitude of the administered dose. Other conditions being equal, the higher the dose, the shorter this period. However, it should be pointed out that the latent period is a relative concept. The more refined our research methods become, the earlier we discover the initial stages of the impact of X-rays. In all probability, changes occur immediately after irradiation, but we do not possess, at the present time, the means by which we would be able to detect the very initial stages of these changes. A further feature of the radiobiological process is the cumulative effect of small doses following shortly one after another. Small doses, given in an interval of time insufficient for the action of the previous dose to have been exhausted, are summed and can result in an effect characteristic of the sum of these doses. Failure to account for the cumulative action of X-rays during the administration of radiotherapy may result in undesirable damage to organs and tissues (see below). The degree of accumulation is apparently different for different types of cells and tissues and may even change for a given tissue depending on its stage of development. Thus, there is a difference in accumulation between resting and germinated seeds. Differences in the cumulative effect between different cells apparently play a significant role in the treatment of malignant neoplasms by the method of protracted fractional irradiation (see below). An extremely characteristic feature of the radiobiological process, which has enormous practical significance, is the different sensitivity of different cells and tissues to X-rays. To one and the same dose, different cells react to a different degree or, which is the same thing, to obtain a certain effect, different doses of X-ray energy must be delivered to different tissues. The essence of this different radiosensitivity is far from fully studied, but there is an undoubted connection between the sensitivity of different cells to X-rays, on the one hand, and the intensity of their proliferative function and the biological processes occurring within them, on the other. This connection finds expression in the so-called Bergonié-Tribondeau law, according to which the radiosensitivity of a cell is higher: 1) the more intense its proliferative function (e.g., malignant neoplasms), 2) the longer its state of karyokinesis continues, 3) the less its morphology and function are definitively fixed (white blood elements). To these signs, one should undoubtedly add the intensity of the physicochemical processes occurring in the cells, which accounts for the special radiosensitivity of a cell with increased function (e.g., cells of the goiter in Basedow's disease, skin in a state of hyperemia, etc.). This fact of the different sensitivity of different cells to X-rays is of paramount importance for radiotherapy, because only thanks to this feature of the radiobiological process do we have the possibility, when irradiating a complex organ constructed of different tissues, to act in a certain way on the cells most sensitive to X-rays, while affecting the remaining, less sensitive ones very little. This phenomenon is designated, not quite accurately, as the elective action of X-rays. Only thanks to the elective action do we have the possibility, when irradiating an organ affected by a malignant neoplasm, to destroy the tumor without destroying the organ itself as a whole and its individual tissues. Below we provide a comparative table of the sensitivity of normal tissues to X-rays (a modification of the Heineke-Perthes table). The sensitivity to X-rays of the skin of the head and trunk of an adult human is taken as the unit of sensitivity in this table. Table of sensitivity of normal tissues to X-rays: Lymphatic (20 and above), Testes and ovarium (3.5), Child's cartilage (2.5), Mucous membrane (2.0), Hair follicle (1.8), Skin of trunk in children (1.6), Intima of blood vessels (1.6), Sweat and sebaceous glands (1.0), Skin of head and trunk (1.0), Parenchyma of liver and kidneys (0.9), Connective tissue (0.7), Muscular tissue (0.3), Skin of face in adults (0.28), Bone tissue (0.25). At one time, the question of the dependence between the radiobiological effect and the wavelength (hardness) of the applied X-ray energy was strongly debated. It was assumed that hard rays possess a lesser biological effect. The latest research, based on precise dosimetric methodology, forces us to assume with greater probability that both the character and the degree of the biological effect, other conditions being equal, depend exclusively on the quantity of X-ray energy delivered to the cell, regardless of the hardness applied. When irradiating any organ located in the depth of the human body, X-rays must pass through the skin. For this reason alone, the reaction of the skin to the impact of X-rays is of special interest to us. Furthermore, as we shall see later, the reaction of the skin to X-rays is taken as the basis for the biological method of measuring X-rays. For these reasons, before setting forth the methods of X-ray dosimetry, we must dwell in more detail on the phenomena of skin reaction under the influence of X-rays (the reaction of other normal and pathological tissues will be set forth below in connection with the radiotherapy of the corresponding organs). Reaction of the 1st degree: upon irradiation of the skin with the maximum permissible (not causing long-term changes) dose of X-rays, often (not always) within the first 24 hours after irradiation, a slight redness appears, and sometimes an edematous swelling of the irradiated area of the skin. This so-called "early reaction" disappears without a trace after 1-2 days. Approximately 8 days after irradiation, the main reaction occurs—reddening of the skin, followed 2-3 weeks later by pigmentation and peeling of the skin. In the initial stage of this main reaction, swelling of the skin follicles, appearing as red dots, is characteristic. Approximately in the 3rd week, hair loss is added, the complete restoration of which occurs within the next 8 weeks. Pigmentation may remain for a long time. The dose causing such a reaction, the so-called erythema dose (ED), is taken as the basis for the biological method of measuring X-rays and is usually designated as HED (Haut-Einheits-Dosis—skin dosimetric unit). A full HED is taken as 100%. With a somewhat smaller dose, we have epilation in the absence of the redness characteristic of the main reaction (suberythematous effect). Reaction of the 2nd degree: with an increase in the dose (by 20-40%), the reaction occurs earlier (after 2 weeks), the redness and swelling are much more intense and painful; with a further increase in the dose, the reaction is accompanied by the formation of blisters (dermatitis bullosa) with sharp peeling of the epidermis and pain. After healing, atrophy of the skin, telangiectasias, and strong pigmentation remain. Hair grows back partially or not at all. Reaction of the 3rd degree: with an increase in the dose up to 80% (burn of the 3rd degree—Röntgen-ulcus). After 1/2-1 week—the same phenomena as in the reaction of the 2nd degree. The redness is patchy with a bluish tint. Deep necroses of the skin. Healing requires a long period (months and even years), often operative intervention is necessary (extirpation and transplantation). Propagation and absorption of X-ray energy. The laws of propagation and absorption of X-rays in the body are of no less importance for the technique and methodology of radiotherapy and X-ray dosimetry than the skin reaction. The intensity of the X-ray energy incident on the body gradually decreases as it passes through it. This decrease occurs for three reasons: 1) according to the law common to all types of radiant energy, the decrease in intensity is inversely proportional to the square of the distance; 2) due to the absorption of X-ray energy by tissue and its conversion into other types of energy; 3) due to the scattering of X-rays. As a result of this decrease in the intensity of X-ray energy in the direction of the depth, the depth dose must constantly remain less than the surface dose, and since the maximum permissible surface dose is the HED, it is consequently below the HED. But for a whole range of diseases, to achieve a sufficient therapeutic effect, it is necessary to deliver to the diseased organ doses close to the HED or (as, for example, in cancer) even slightly exceeding this dose. To achieve this goal, a special irradiation technique is used, which increases the "depth coefficient," i.e., increases the ratio between the surface dose and the dose in the depth of the body. The disadvantageous influence on the depth dose, consisting in the decrease of intensity with the square of the distance, is reduced with an increase in the focal distance (a simple geometric calculation). In connection with this, in deep radiotherapy, a focal distance of up to 1 m is used.

The disadvantageous influence of X-ray energy absorption by surface layers can also be significantly reduced by increasing the hardness of X-rays. The absorption of X-ray energy depends on: a) the chemical composition of the absorbing body (in this respect, the human body, with the exception of bones, can be equated to distilled water; this condition is not subject to arbitrary change); b) the hardness of the X-rays—the harder the rays, the less their absorption. By increasing the hardness of X-rays, we achieve the result that a smaller quantity of them is absorbed by the surface layers and more reaches the organ located at depth, upon which we wish to act. In connection with the dependence of X-ray radiation hardness on the voltage at the poles of the X-ray tube, voltages of 180-220 kV are used in deep therapy. Filtration of the X-ray beam emanating from the tube also has a significant influence on the hardness of the X-ray radiation and, consequently, on the depth coefficient. The X-ray radiation obtained from the tube is not homogeneous, but represents a mixture of rays of different wavelengths. The soft rays included in the composition of this heterogeneous beam are absorbed almost entirely by the upper layers of the body, mainly by the skin, which is thus relatively early saturated to the maximum dose (HED) and serves as a barrier to further irradiation. By placing metal filters in the path of the beam, which absorb only the soft rays that burden the skin, we gain the possibility of irradiating the given field for longer and, accordingly, delivering a greater quantity of energy to the depth to the diseased organ. In practice, in deep therapy, a filter of 0.5 mm of zinc or copper is usually used. These filters, at the usual hardness of 180-200 kV, produce so-called "practical" homogenization of X-rays, i.e., after such filtration, the rays in practice penetrate to the depth as homogeneous rays. For special purposes (see below, the Coutard method in X-ray therapy of carcinomas), even thicker filters are used. In superficial therapy with a voltage of 80-100 kV, aluminum filters with a thickness of 0.5-1.0-3.0 mm are used. A huge role in the matter of increasing the depth coefficient is played by the use of the phenomenon of X-ray scattering. This phenomenon consists in the fact that X-rays propagating in a straight line are partially deflected from this path, "thrown out of it," and scattered. Each element of the irradiated body thereby becomes, as it were, a source of new radiation—secondary scattered rays, which differ from the primary radiation not only in their direction but also in their hardness (the rays thereby become to a greater or lesser degree softer—the Compton effect). Unlike absorption ("pure absorption"), there occurs a relatively small decrease in X-ray energy, and mainly a redistribution of it in space. Unlike the X-rays absorbed in the overlying layers, the scattered radiation is not lost for the therapeutic effect at depth. On the contrary, this radiation is directed back into the surrounding tissue, is partially absorbed there, and thus significantly increases the depth dose (Streuzusatzdosis—Friedrich's additional dose). The magnitude of this additional dose grows with an increase in the hardness of X-rays (a condition, of course, fulfilled in deep therapy) and with an increase in the field of illumination to dimensions of 20x20 cm (more correctly, with an increase in the volume of the irradiated body). Increasing the hardness, filtration, increasing the focal distance, and the size of the field, along with the method of multi-field illumination (see below), place in our hands methods for bringing the dose at depth to the levels necessary for a therapeutic effect, without exceeding the skin's tolerance limit with the load. As can be seen from the above, the magnitude of the X-ray energy absorbed by the tissue—the dose—plays a paramount role in the radiobiological effect. Therefore, it is understandable that special attention was paid to the development of the technique and methodology for measuring the X-ray dose (dosimetry) already in the early stages of radiotherapy. In radiotherapy, especially deep radiotherapy, we are interested not only in the quantity of energy on the surface of the irradiated part of the body (surface dose), but no less in the quantity of energy that is delivered to the depth and absorbed by the organ upon which we strive to act therapeutically (depth dose). This latter, along with other factors (focal distance, size of the illumination field), primarily depends on the hardness of the X-ray radiation used. In connection with this, X-ray dosimetry is divided into quantimetry—the measurement of the quantity of X-ray energy—and qualimetry—the measurement of the quality (hardness) of X-ray energy. Quantimetry. The task of measuring the quantity of X-ray energy encountered significant difficulties, rooted in the complexity of the problem of the propagation of X-rays in the depth of tissues and its conversion into other types of energy. These difficulties consist in the fact that in X-ray dosimetry, we are dealing not with a ponderable mass, but with a flux of energy, which propagates in a relatively complex manner in the body upon which it falls, partially passes through it, as a result of which only a part of the energy falling on the body remains in the body and exerts a biological effect. The measurement of absorbed X-ray energy in energy units, in connection with the small quantities of energy with which one has to deal here, and for a number of other physical reasons specific to X-rays, is so complex that it is feasible only under experimental conditions in a physics laboratory, and therefore is not suitable for everyday practice. Therefore, from the very beginning, it was necessary to resort to the reactions caused by X-rays as a dosimetric factor, the degree of which stands in a definite dependence on the intensity of X-ray energy. Of the numerous methods of this kind proposed, the Holzknecht and Sabouraud-Noiré methods and the ionization method are currently used in practice. The Sabouraud-Noiré method is based on the property of barium platinocyanide to gradually change its light-green color to light-yellow to brownish under the influence of illumination by X-rays. (The reasons for this change of color lie in the separation of water of crystallization.) The S-N radiometer has the form of a notebook containing stamped, rounded, flat tablets of barium platinocyanide, some of which are placed during irradiation at half the distance between the anticathode of the tube and the skin. On one side of this notebook are placed 2 colored squares, of which one (Teint "A") shows the normal color of an unirradiated tablet, and the other (Teint "B")—the color of the tablet after irradiation with its so-called full S-N dose. For the possibility of using also the colorings of the tablet intermediate between Teint "A" and "B" for the purposes of counting fractional doses from the full S-N dose, Holzknecht proposed a color scale and divided this dose into five units (H-Holzknecht-Einheit): 1 S-N=5H. Since the processes of absorption of X-rays by animal tissues and by barium platinocyanide differ from each other, dosing with the help of an S-N tablet does not give an idea of the X-ray energy absorbed by the body. For this same reason, the readings of the S-N dosimeter (as well as the Holzknecht dosimeter) strongly depend on the hardness of the X-ray energy. One S-N=5H (Teint "B") corresponds to the maximum dose, i.e., it causes a reaction of the 1st degree only when using unfiltered rays of medium hardness. When using harder radiation, the quantity of "H" corresponding to the maximum dose increases. According to the indications of the Holzknecht scale for rays of medium hardness, filtered by 3 mm Al, this maximum dose = 8H, and for the hardness and filtration used in deep radiotherapy (170-180 kV, filter 0.5 mm Cu or Zn), this dose (HED) = 12H. In view of all these considerations, the S-N method is at the present time supplanted by a more perfect method based on ionization, and has retained its significance to a certain degree only for superficial (skin) therapy. All ionization instruments are based on the property of X-rays to ionize air and thus make it a conductor of electricity. In principle, every ionization instrument consists of an electrometer, the movable strip of which, upon its charging, moves away (due to charging with like electricity) from the stationary one. If X-rays enter the air space between both strips, the gas atoms are ionized, the air becomes electrically conductive, the electric charge flows away, and the movable strip of the electrometer gradually returns to its initial position. The more intense the irradiation, the faster the discharge of the electrometer occurs, and the faster the reverse movement of the aforementioned strip. The speed (time) of the reverse movement of this strip thus serves as a measure of the intensity of X-ray energy. In practice, an ionization chamber of small size (thimble chamber) is used, in which there is a system built on the principle of a capacitor and connected by a long cable, protected from X-rays, to an electrometer. The movable part of the electrometer has the form of a needle or a fiber, shifting along a graduated scale.

During measurements, a stopwatch is used to set the time required for the filament or needle to pass over a certain part of the scale. This time serves as a measure of the intensity of X-ray energy. With the help of these instruments, the time required to obtain a dose equal to the HED under certain irradiation conditions is established before the patient is irradiated, and the irradiation of the patient is then performed based on time.

Instruments of the newest type (Siemens Dosismesser, Strauss Mecapion) allow for monitoring the dose during the entire time of irradiation. In these instruments, unlike those described above, not an electroscope is used, but a vacuum tube galvanometer, which directly measures the ionization current, which in turn is amplified (approximately 100,000 times) with the help of an amplifier tube.

An ionization chamber, remaining on the surface of the irradiated area for the entire duration of irradiation, thus allows for monitoring the constancy of the intensity of X-ray energy falling on the body throughout the entire session, and even the magnitude of the dose already delivered at a given moment (integral ionometers). An extraordinary advantage of the newest ionization chambers is the independence of their readings from the hardness of the measured X-ray energy. (See also X-ray technology.)

In connection with the improvement of ionization instruments, it became possible to replace the insufficiently accurate biological unit of X-ray energy intensity, which is the HED, with a physical unit based on precise principles. The definition of this unit, as it was adopted by the last International X-ray Congress, states: "The absolute unit of X-ray dose is delivered by the quantity of X-ray energy which, when irradiating 1 cm³ of air at a temperature of 18°, a pressure of 760 mm of mercury, with full utilization of electrons formed in the air, and with the exclusion of the influence of the chamber walls, gives a conductivity, as a result of which the measurement at saturation current shows a quantity of electricity equal to 1 electrostatic unit."

This unit is called 1 Röntgen and is abbreviated with the letter r. All modern ionization dosimeters are calibrated in "r" units. HED (under conditions of deep therapy) = approximately 600 r. When using softer rays, the maximum dose is, in all probability, somewhat lower than 600 r (this question has not yet been finally clarified).

Qualimetry. The hardness of X-ray radiation is determined by the magnitude of the voltage applied to the poles of the X-ray tube. Strictly theoretically, this voltage (maximum voltage kV_max) determines only the wavelength of the hardest component of the radiation. According to the Duane-Hunt formula, Vλ_min = 12.35, in which V signifies the maximum voltage in kilovolts, and λ_min the shortest wavelength of the given radiation in Angstrom units.

Otherwise, the composition of the heterogeneous beam emitted by the tube also depends on the material of the anticathode (in modern X-ray therapy tubes, usually tungsten) and on the character of the high-voltage curve (on the type of apparatus). If the maximum voltage characterizes the short-wave end of the X-ray spectrum quite definitely, then, on the other hand, the filter used characterizes its long-wave boundary with accuracy sufficient for practice. Thus, for an apparatus of a certain type, the filter and the maximum voltage fully determine the composition of the given radiation and, in connection with this, the conditions of its distribution when passing through the body.

Therefore, special attention was paid to the development of methods for measuring the voltage at the ends of the tube. The determination of this voltage is associated with significant difficulties, since we are dealing here with high voltage, for the measurement of which there are practically no satisfactory measuring instruments in technology. An extremely convenient method for determining voltage is the measurement, with the help of a voltmeter, of the voltage that exists at the ends of the primary winding of the transformer and by which, for a given apparatus, the high voltage at the ends of the secondary winding is determined. The scales of these voltmeters (bearing in practice the name kilovoltmeters) are calibrated in kilovolts by the more accurate methods of measuring high voltage described below. The inaccuracy of these instruments depends on the fact that they do not take into account the voltage drop with load (milliamperage) and losses in the wiring.

A simple, but much more accurate method is the direct measurement of high voltage at the ends of the X-ray tube with the help of a sphere spark gap (usually spheres with a diameter of 25 cm are used). Below is a table for determining the magnitude of high voltage (kilovolts) depending on the spark length between spheres with a diameter of 25 cm. Spark length in cm: 0.3, 0.4, 2.0. Voltage in kV: 11.3, 14.4, 20.4, 26.5, 31.8, 60.5. Spark length in cm: 3.0, 5.0, 7.0, 9.0, 10.0. Voltage in kV: 87.3.

247 The most accurate indirect method for measuring the voltage at the ends of the tube is the spectroscopic decomposition of the X-ray beam by means of a crystal (Seemann's and March's, Staunig's and Pritz's spectroscopes). On such a spectrogram, the length of the shortest wavelength λ_min in the given radiation can be determined with great accuracy, and then the maximum voltage (V_max) according to the above-mentioned Duan-Hunt formula. In recent times, the method of determining the hardness of X-ray radiation by measuring its degree of absorption in copper has become most widespread. The thickness of a copper layer that absorbs half of the given radiation—the 'half-value layer' (Halbwertschicht)—is determined by the ionization method described below. In these measurements, a working (homogenizing) filter must necessarily be placed between the tube and the measuring copper layer. Tables have been compiled that allow, based on data about the filter and the magnitude of the 'half-value layer' in copper, to determine the high voltage at the ends of the tube. But what is even more important for dosimetry (determination of depth dose)—different radiations having the same half-value layer are distributed identically in the body regardless of the type of apparatus (Halthusen, Liechti). The above-mentioned methods for measuring the intensity and hardness of X-ray energy now allow, with considerable accuracy, the determination not only of surface but also of depth doses. The comparatively rarely used method for measuring depth dose is the direct measurement of dose at the depth, at the site of the pathological focus. Such direct measurement, as is self-evident, is possible only where the diseased organs are connected with the external space by natural openings (insertion of an ionization chamber into the uterine cavity, into the rectum). In other cases, for determining depth dose, phantoms made of materials identical to the human body in terms of X-ray absorption (water and wax phantoms) are used. With the help of these phantoms, the dose at depth is determined under various irradiation conditions used in practice at a given X-ray institution, and the data obtained serve as the basis for determining the depth dose when irradiating the patient. Tables (Volz, Grebe and Nitzge) or diagrams with curves (Dessauer and Vierheller, Holfelder), developed in physical laboratories, have found wide practical use, which provide the magnitude of the dose from centimeter to centimeter in depth under the most varied irradiation conditions (different voltages, focal distances, and field sizes). The technique of radiotherapy, i.e., the magnitude of the dose used, its distribution over time, repetition of irradiation, intervals between individual irradiations, varies in each case depending on the technical conditions (location of the focus), the nature of the pathological process, and partly on the individual characteristics of the given patient. This technique in the field of deep therapy has changed significantly over the years. The technique of superficial R. has undergone comparatively little change over decades. Radiation of medium hardness (70-100 kV) is used, with filters of 0.5-1.0-3.0 mm Al; unfiltered rays are almost never used. The maximum dose (erythema dose = ED) in full dose (dosi plena) in one session (seance) is rarely used. Usually 1/3 ED is given with repetition after 1-2 weeks (dosis refracta). After 3 sessions (=1 series), an interval of 3-4 weeks. After the second series, the interval is usually increased. The focal distance is usually 23-30 cm. For skin therapy with processes spread over large areas or even the entire body, partially overlapping fields with a diameter of approximately 30 cm are used. For epilation of the hairy part of the head, 4-5 fields are used with a dose of 0.7-0.8 ED per field, with filtration of 0.5-1.0 mm Al. Parts of the body not to be irradiated, mainly parts especially sensitive to X-rays (hair covering, sex glands, eye, larynx, endocrine glands), are covered with protective (lead-rubber) rubber. The technique of deep therapy is considerably more complex. In connection with the evolution of views on the biological action of X-rays on pathological processes, especially on malignant neoplasms, or in connection with improvements in X-ray apparatus, this technique has gradually changed and is still in a state of evolution (the technique of fractionated prolonged irradiation in carcinomas). In connection with the task of acting on pathological processes located deep in the body and the need for this purpose of hard radiation, a voltage of 180-220 kV is used. The beam of rays is homogenized by a filter of 0.5 Cu or 0.5 Zn. Depending on the nature of the pathological process, the magnitude of the dose and its distribution over time (massive or fractional doses) are determined. There, where, as in malignant neoplasms, it is necessary to deliver significant doses to the focus (according to the method of intensive R., minimum 110% HED in a short period of time), multi-field irradiation with concentration of rays from all fields in the area of the focus ('crossfire') is used. The location of these fields on the skin and the direction of the rays are dictated by the location of the focus, while the number and size of the fields and the focal distance are determined by the dose that should be delivered to the focus according to the nature of the disease. Thus, each case of such intensive irradiation represents a special problem requiring the compilation of a special plan taking into account all the individual characteristics of the case, first of all the exact anatomotopographic determination of the position of the pathological focus. In this regard, in addition to the above-mentioned depth dose tables, special anatomotopographic sketches and templates (the best known are Holfelder's templates) serve as assistance. Re-irradiation of the same field, after it has been irradiated with a full HED, is not permissible earlier than six weeks later. Subsequently, the intervals should be increased. Non-compliance with these rules results in damage to the skin. In the very recent time, a significant revolution has occurred in the technique of R. of malignant tumors, consisting mainly in the replacement of the method of intensive therapy with large single-session doses by the method of irradiation with prolonged fractional doses (see in detail below). It is also appropriate here to mention the use in recent years in R. (skin diseases, diseases of the cornea of the eye, partly in bronchial asthma, gastric ulcer) of ultra-soft rays, the so-called Buchi rays, obtained in special X-ray tubes at voltages of 6-10 kV. These rays are absorbed in the most superficial layers of the skin, do not cause epilation, and, according to Buchi, are not capable of causing damage to the skin. Under such conditions, their definite effect on internal processes (in gastric ulcer, etc.)—a decrease in the number of leukocytes in the blood soon after irradiation—should be explained by the influence of these rays on the endings of the autonomic nervous system embedded in the skin (reflex effect). The nature and significance of these rays in therapy are still insufficiently clarified. Damage caused by X-rays. As is evident from the foregoing, X-rays are a strongly acting agent capable of affecting all organs and tissues of the human organism. It is therefore understandable that with incorrect application in therapy or with careless handling of them (doctors, X-ray technicians), more or less severe damage to the organism may occur. In the first years of the use of X-rays in medicine, our knowledge of these damages was limited mainly to changes in the skin. But in subsequent years, especially with the development of deep R., pathological changes in a number of internal organs began to be revealed, undoubtedly connected with the harmful effect of X-rays. All these damages in some cases are caused by the delivery to an organ of a dose exceeding its tolerance to X-rays (overdosage due to inaccurate dosimetry, non-use of a filter, erroneous repeated irradiation of the same field). This also includes insufficient attention to the increased sensitivity of the skin under special conditions (in the island-like inflammatory state, in Basedow's disease, etc.). To this category should also be included damage to the skin that may occur even after the delivery of a dose not exceeding the tolerance limit, if shortly after irradiation the same area of skin is subjected to additional exposure by another agent (mechanical friction of clothing or bandages, thermal action of compresses or sunlight, chemical action of irritating ointments, etc.). All these cases result in the relatively rapid onset of acute phenomena. In other cases, the damages are the result of chronic exposure to X-rays over a long period of time (months and years). The doses received at one time may be very small, but, due to the cumulative effect of X-rays, they can ultimately cause significant, often irreparable and life-threatening damages.

Such are the damages from numerous repeated irradiations, especially when adequate intervals between individual series are not observed, and mainly professional damages in persons working for a long time in the field of X-rays without sufficient protective devices (doctors, X-ray nurses, X-ray technicians, workers in X-ray tube factories). In these cases, the damages occur comparatively late, often even after a considerable period of time (years) after the cessation of the direct action of X-rays ('late damages'—'Spätschädigung' of German authors). As for the damages to the skin, the organ most thoroughly investigated in this respect, the picture of acute damages to it (burns) is comparatively simple and has already been described in detail above. Much more diverse are the chronic changes in the skin that result from prolonged exposure to X-rays and are found almost exclusively as professional damages to the hands of doctors and X-ray technicians. These changes are characterized by a peculiar dystrophy of the skin (Kienbock). The skin is dry, inelastic (atrophy of sweat and sebaceous glands), thickened in places, covered with hyperkeratoses and pigmented. The nails become grooved, brittle, and under the edge of the nails there appear peculiar accumulations of epidermis masses, sometimes passing into painful warty formations. Later, extremely painful cracks that stubbornly resist treatment, thickenings, and ankyloses of the finger joints develop. The basis of these changes lies mainly in persistent changes in the blood vessels (endothelium of capillaries). On the basis of these chronic changes, skin cancers often develop, giving numerous metastases. As early as 1911, statistics (Hesse) could count 54 cases of such cancers, of which 50 were of a professional nature. In the last 2 decades, a whole series of cases have been added to this number. Another frequently encountered form of late skin damage, usually after repeated irradiations with hard rays, is the so-called chronic indurative edema of the skin (Jungling). This form is characterized by the appearance after several months, and sometimes even after 1-1/2 years after the last irradiation, of dense infiltrates in the form of plaques several centimeters in diameter in the skin and subcutaneous fatty tissue. These infiltrates are an absolute contraindication to further irradiation of the affected areas of the skin due to the danger of severe ulcerations. The basis of these infiltrates is chronic inflammation (necrosis) of the subcutaneous fatty tissue as a result of severe changes in the blood and lymph vessels. Due to these deep changes in the blood vessels (capillaries), any intensely and repeatedly irradiated area represents a locus minoris resistentiae, on which even after a considerable period of time under unfavorable conditions (trauma, etc.) an ulcer may form. Among the internal organs in terms of the danger of damage from X-rays, the first place is occupied by the blood-forming organs and the sex glands due to their high sensitivity to X-rays. Damage to the blood-forming organs is expressed in pathological changes in the composition of the blood, mainly its white elements. When large areas of the body are irradiated with hard rays, as a result of the destruction of leukocytes that are very sensitive to X-rays, leukopenia occurs, which depending on the degree of damage (and partly on the nature of the underlying disease) lasts for a longer or shorter time. In patients with a favorable prognosis for the underlying disease, the number of leukocytes returns to normal within 2-3 months. Much more persistent are the blood changes found as professional damages in persons working for a long time in the field of X-rays. Here also, a more or less significant persistent leukopenia comes to the fore, which can improve to a certain extent when work with X-rays is interrupted. In other cases, a mild degree of general anemia and eosinophilia are noted. Sometimes these blood changes pass into leukemia or aplastic anemia, from which patients die. As for the damage to the sex glands, after intense irradiation of the scrotum, azoospermia may occur, which usually disappears after several months. Much more persistent are the changes that occur after prolonged exposure to small doses, as is the case with professional work with X-rays. In these cases, azoo-, oligo-, and necrospermia are observed. But even in these cases, when work with X-rays is discontinued for a long period, the normal function of the sex gland can be restored (in one case only after 6 years). The offspring of such people, according to available observations, show no abnormalities that could be associated with damage to the germ cells. The situation is analogous with the female sex glands. In the last decade, a number of cases of larynx damage have been published, indicating the extreme sensitivity of this organ to X-rays. Here we are not referring to the dryness and hoarseness that occur soon after irradiation and disappear relatively quickly. These symptoms belong to the phenomena of 'early reaction' (see above). To the early reaction should also be attributed the life-threatening stenoses resulting from laryngeal edema. The damages referred to here belong to the 'late damages' that occur many months after irradiation and consist of perichondritis with necrosis of the larynx and often end fatally. These phenomena occur with doses not exceeding 1 HED. Prevention is protection (covering the larynx) during irradiation of the neck area, and for the larynx itself—doses not exceeding 60-70% HED. Undoubtedly, the intestine, under unfavorable circumstances, can suffer from the action of X-rays. The intestinal pains and diarrhea sometimes observed with intense irradiation of the abdomen are probably connected with this harmful influence. In more serious cases, we also encounter bloody diarrhea. Finally, cases of necrosis of parts of the intestine with subsequent perforation have been described. These cases are probably the result of the intestinal loop being repeatedly exposed to the beam of rays in multipole cross-irradiation. In other cases, adhesions may form that can later cause painful symptoms. According to Seitz and Wintz, this harmful dose for the intestine (Darmdosis) = 130% HED. Irradiation should be technically arranged to avoid such a dose concentration on the intestine. As for the skeletal system, only individual cases of bone necrosis after X-ray irradiation have been described, but it is doubtful whether these necroses are in direct connection with the action of X-rays. Undoubtedly, X-rays have a delaying effect on bone growth in young age (irradiation of the epiphyseal cartilage area). Cases of damage to the eyeball by X-rays (clouding and ulceration of the cornea, formation of cataracts) have been described. Undoubted cases of indurative changes in the lung after intense R. for cancer of the breast gland are known. Changes in the urinary bladder under the action of X-rays are rarely observed, unlike radium rays, in the application of which sometimes marked changes occur. Among the more general damages experimentally proven are damages from intense irradiation of the reticulo-endothelial system. Among the harmful side effects on the nervous system, vomiting in children during head irradiation for epilation (irritation of the brain membranes?) should be noted. During epilation of the hairy part of the face, a harmful side effect on the salivary glands appears; dryness in the mouth, and sometimes also symptoms of stomatitis as a result of decreased or complete cessation of secretion of the salivary glands. Therefore, between the irradiation of both halves of the face, a minimum interval of 8 days is mandatory. Prevention of the above-mentioned damages in patients undergoing R. consists in strict observance of all rules for the rational conduct of irradiation. As for professional damages, as far as R. is concerned, it is possible to organize it technically (unlike X-ray diagnostics, especially fluoroscopy) in such a way that workers remain completely outside the sphere of influence of X-rays. This is achieved by a series of protective measures. The room in which irradiation is carried out is isolated in X-ray respect from adjacent rooms, as well as from the room where the medical personnel are located, by protective walls covered with a 5 mm thick layer of lead. Observations of patients and instruments are made through special lead glass. In recent years, so-called self-protective tubes have been used, having a narrow opening for the release of only the therapeutic beam of rays. The mandatory use of fully adequate protective devices in X-ray institutions is prescribed by legislation, and every X-ray worker has the right to refuse to work in their absence. Taking into account the professional harmfulness of work with X-rays, the NKT USSR issued a resolution on the protection of labor for radiologists (see Röntgentechnik). Radiotherapy in dermatology. R. of skin diseases was first carried out exclusively according to the type of surface therapy (soft, unfiltered or weakly filtered rays).

But as our knowledge of the essence of skin diseases deepened and it became clear that in a number of skin diseases the pathological-anatomical process is located not only in the superficial but also in the deeper layers of the skin, harder rays and more intense filtration began to be applied depending on the case. In dermatological practice, the method of deep therapy has not taken root mainly because this produces an undesirable side reaction from deeply located organs. The typical method of deep therapy is applied in dermatology only in cases of indirect therapy: in illuminating the thymus in psoriasis according to Broca's method or in irradiating the spinal ganglia in lichen ruber, recommended by French authors. To prevent damage, along with correct technical conditions of irradiation (dosage, filtration, etc.), the history (previous irradiations, treatment with irritating ointments), absence of additional irritations during treatment (sun baths, unsuitable ointments, etc.), and correct intervals between individual sessions and series play a large role. In terms of indications for the application of radiology, skin diseases should be divided into 3 groups. I. Indicatio primi ordinis. This group includes those diseases in which R. is the best method of treatment (the method of choice): acne vulgaris, condylomata acuminata, congelatio (perniones), dermatitis papillaris capillitii, ekzema subacutum, chronicum, seborrhoicum. All forms of eczema, except acute ones, are grateful objects for R. Often healing is observed after prolonged unsuccessful treatment with ointments, before which R. has the additional advantage of greater convenience (cleanliness). As a result of radiotherapy, there is a decrease (sometimes after initial intensification), and later also disappearance of itching. Weeping eczemas dry up, keratoses disappear. In favus, trichophytia, mikrosporia, sycosis parasitaria, treatment consists in complete epilation. In trichophytia profunda, the resorptive effect of X-rays on inflammatory infiltrates also plays some role. In hyperidrosis, as a result of irradiation, atrophy of the sweat glands occurs. In keloides (scarring), leukoplakia, mycosis fungoides, pityriasis rosea, prurigo, pruritus ani, vulvae, a satisfactory effect is also obtained. R. in psoriasis gives excellent results in all stages, but long-term healing is not achieved. The irradiation of the thymus proposed by Broca as causal (?) therapy has not received widespread acceptance. In sycosis simplex, healing is achieved (epilation). II. Indicatio secundi ordinis. This group includes skin diseases in which R. is equivalent to other methods of treatment: acne rosacea, bubones, induratio penis plastica, lichen ruber planus, acuminatus, lichen simplex chron. Vidal (neurodermitis circumscripta). In the latter form, the French have proposed irradiation of the spinal ganglia. III. Indicatio tertii ordinis. This group includes skin diseases in which R. is an additional auxiliary means or is tried when other methods of treatment fail: angioma (haemangioma, naevus vascularis), clavus, cornu cutaneum, ichthyosis, sclerodermia. Radiation therapy in gynecology. Diseases of the female genital sphere, in which treatment with X-rays is applied, can be divided into 2 large groups. The first includes painful phenomena directly dependent on the disorder of the endocrine function of the ovaries and manifested mainly in the disorder of the menstrual function (intensification, weakening or complete disappearance of menstruation). The formation and growth of myomas also belong here. The second group includes pathological symptoms standing only in an indirect connection with the disease of the ovaries and having as their direct cause the disorder of the function of the so-called complementary glands, mainly the hypophysis and thyroid gland (this includes chlorosis, osteomalacia, painful phenomena in the climacteric and others). The task of R. in such disorders consists in lowering the function in the case of hyperfunction, and in the case of hypofunction—in stimulating the activity of the gland, if one recognizes a biopositive effect for X-rays at all. The matter is completely different with disorders of the endocrine function of the ovaries. The latter are an internal secretory organ, the function of which has a cyclical nature, unlike other endocrine glands. The fact is that one of the main functions of the ovaries—regulation of processes in the uterine mucosa—proceeds not with continuous uniformity, but represents a periodic process, individual phases of which differ from each other not quantitatively but qualitatively. In direct causal connection with these periodic changes in the ovaries stand certain cyclical changes in the uterine mucosa, on the one hand, and on the other hand, the preservation of the normal form and size of the uterus depends on them. Various diseases of the uterus, such as disorder of the menstrual cycle (amenorrhea, menorrhagia, etc.), as well as changes in the uterus itself (myomas), are often caused not by a simple hyperfunction or hypofunction of the ovary, but by a disorder in the course of these periodic anatomophysiological processes of the ovary. Therefore, the role of X-rays in diseases of the ovary and uterus consists not so much in increasing or decreasing the function, but in a corrective influence, the aim of which is to restore the normal order of the periodic processes characteristic of the ovary. After

Halberstadter in 1905 first pointed to changes in the ovaries of rabbits after irradiation with X-rays. The effect of X-rays on the ovaries was thoroughly studied both from the anat.-histological standpoint and from the standpoint of the various functional changes caused by such irradiation. For the nature of these changes, the primary importance is the significant difference that exists between the individual cellular elements of the ovary in terms of sensitivity to X-rays. The greatest sensitivity is possessed by Graafian follicles, less by primordial follicles, and even less by the germinal epithelium. This difference is manifested in the size of the dose required to destroy these elements. By applying various doses of X-rays, we are able within certain limits to modify the anatomical and the associated functional effect of irradiation. Vinz distinguishes 3 degrees of action of X-rays on the ovaries: 1) When a dose of 45% HED is applied, all endocrine elements of the ovary die, leaving only the scar-modified connective tissue basis of the ovary; the result is complete castration, fully analogous to castration by operation. 2) Under the influence of a dose of 34% HED, all reproductive elements of the ovary die, leaving only the endocrine elements originating from the theca folliculi. Ovulation and formation of the corpus luteum are no longer possible. The consequence of such irradiation is prolonged amenorrhea with relatively moderate symptoms of atrophy. 3) When a dose of 28% HED is applied, we obtain only temporary amenorrhea (temporary sterilization), since at this dose the less sensitive to X-rays primordial follicles do not perish. Therefore, when these follicles mature, ovulation begins again, menstruation appears, and thus full possibility for pregnancy is given. From the foregoing it is clear that among diseases directly related to disorders of ovarian function, the most favorable objects for treatment with X-rays are menorrhagias, metrorrhagias, and myomas. For this it is sufficient to apply a dose of 34% HED to the ovaries, which results in the destruction of the follicular apparatus, cessation of ovarian function, cessation of menstruation, and consequently also pathological uterine bleeding. Usually after irradiation menstruation still occurs once or twice, more rarely three times, after which it ceases forever. On the same principle of cessation of ovulation is based R. of myomas. The connection between the development and growth of myomas and the processes of ovulation is undeniable. With the onset of climacteric, myomatous tumors usually shrink and disappear. The same occurs with the application of R. After X-ray castration, myomas significantly decrease in volume within the next few months. However, it should be noted that, according to some authors, we are dealing here also with the direct action of X-rays on the myomatous tumor itself. -Strictly speaking, the term 'castration' for the described effect of X-ray irradiation is not quite appropriate, because despite the cessation of ovulation, the role of the irradiated ovary in the endocrine relation for the organism is not yet finished. This circumstance finds its expression in much less intense, than in operative castration, symptoms of atrophy, and mainly in the absence of severe atrophic changes in the sexual organs. In view of this, the entire process is more correctly designated by the term 'X-ray sterilization' or 'ex-ovulation.' The success of radiotherapy in these cases is 100%. The danger quoad vitam is zero. With modern technique, all treatment reduces to one series, usually consisting of 4 sessions. As climacterium approaches, the dose necessary to obtain the effect decreases and falls to 20% HED. In young women, due to the undesirability of long-term shutdown of ovarian function, the method of so-called temporary sterilization is used. With the help of a lower dose (according to Vinz-28% HED), an attempt is made to destroy only the Graafian and the most mature primordial follicles, leaving untouched the other specific elements of the ovary, which as they mature restore ovarian function. With this method, it is possible to achieve temporary (for 1-2 years) cessation of menstruation and the pathological bleedings associated with myomas and metropathies. The difficulty lies in the danger, due to undoubtedly existing individual differences in the sensitivity of the ovaries to X-rays, of obtaining in some cases undesirable prolonged sterilization. On the other hand, there are fears of the appearance of offspring with developmental defects, due to fertilization and development of eggs partially damaged by X-rays. The number of such cases published in the literature is small, and moreover, in these cases the connection between the malformation and the previous irradiation is still questionable. But since in experiments on animals such malformations after irradiation have undoubtedly been obtained, the question of the permissibility of the application of temporary sterilization in humans cannot yet be considered resolved. There is no doubt about the inadmissibility of the method of temporary sterilization as a contraceptive (see) due to the danger of prolonged castration and the profound changes caused in the organism by the shutdown of ovarian function. When it is necessary to stop abundant, sometimes even directly life-threatening uterine bleedings in severely anemic patients from previous chronic blood loss as quickly as possible, irradiation of the spleen with small doses of 5-10% HED (increase in blood clotting) is occasionally applied with success. Less reliable are the results obtained when using R. in cases of amenorrhea. Undoubtedly, in a considerable number of cases, irradiation of the ovaries with small doses succeeds in restoring menstrual function. As for the mechanism of action of X-rays in these cases, the most justified views seem to be those of Borak, according to which the cause of amenorrhea in a number of cases is too slow development of defective follicles, which hinder the following normal follicles from developing freely (persistierende Follikel). Under the influence of X-rays, these defective follicles, which have increased sensitivity to X-rays, degenerate, which removes the obstacle to the development of subsequent normal follicles ('elimination therapy'). In other cases, elimination of amenorrhea is achieved by irradiation with small doses of the spleen or liver (destruction of defective follicles by products of protein breakdown?). Finally, in a number of cases of amenorrhea, a favorable result is achieved by irradiation of the pituitary gland (cause of amenorrhea--increased function of the pituitary gland). The definite effect achieved by irradiation, mainly of the pituitary gland, and also of the thyroid gland, in cases of severe symptoms of atrophy in climacterium (Borak, Kaplan, Prokhovnik and others), is explained by the reduction of hyperfunction of these so-called complementary glands. Here it is also appropriate to mention that attempts to achieve castration by irradiation of the pituitary gland (pituitary castration-Hirsch, Hofbauer) were not successful. In conclusion, mention should still be made of the application of R. in osteomalacia (sterilization). In a number of cases, it is possible to achieve so-called complete healing or at least significant improvements. Radiotherapy in surgical diseases. In this field, R. is most frequently and widely applied in malignant tumors. To this day, in many cases of cancer, under certain indications, the knife holds first place, but the successes of R. in recent years have forced many authors to reconsider the question, and in a considerable number of cases of cancer, even in an operable stage (for example cancer of the larynx, tongue), has become entirely an object of R. In inoperable cases of malignant tumors, the only and obligatory method of treatment is R. or radiotherapy, provided there are no special contraindications. Observations on the process of treatment of malignant tumors lead to the conclusion that the therapeutic effect depends almost entirely on the local destruction of malignant cells by X-rays. To many authors it seemed that the problem of treating cancer with X-rays reduced to the technical task of inventing powerful apparatus and tubes and finding such a dose that leads to the complete destruction of the cancerous or sarcomatous cell. However, the cancerous and sarcomatous doses established by German authors (Friedrich, Kronig, Seitz, Wintz) gave an effect only in a small number of cases; in most cases, a larger dose is required to destroy tumors, while in others, on the contrary, an effect may be obtained from a smaller dose. The treatment of cancer with X-rays cannot be conceived as a purely mechanical process. Each case of cancer or sarcoma must be considered as something individual. The carcinomatous and sarcomatous doses play the role of a certain guiding average value, which should be followed in treatment. Treatment with X-rays, besides the local effect on the tumor, is also accompanied by the action of the rays on the tissues neighboring the tumor.

A significant role in this process is played by the effect on the surrounding connective tissue, causing its proliferation between the remnants of the tumor and newly formed vessels, which ultimately leads to the formation of a scar in place of the tumor. X-rays also have a general effect on the body during treatment, which is caused by: 1) absorption of breakdown products from the irradiated area, 2) the direct action of rays on the vessels in the irradiated area and their contents—blood cell elements, and 3) the influence of rays on nerves and endocrine glands. In treatment, it is necessary to seriously consider the factor of general influence, as there are cases where, with the complete destruction of the tumor, the patient dies from x-ray cachexia. Taking this phenomenon into account, it is necessary to spare the patient's strength and, accordingly, plan the treatment. Macroscopic changes caused by x-rays in tumors consist in the fact that in the first days of treatment, tumors, especially those rich in blood, become edematous, and in ulcerated ones—discharge increases. Often these phenomena are accompanied by pain, a feeling of tension in the tumor, and an increase in temperature. In favorable cases, the tumor decreases already during the treatment period or after 2-4 weeks. With a good outcome, the tumor shrinks more and more and is finally replaced by scar tissue. In cases of ulceration, under the influence of radiation therapy, fresh granulations form, and then the ulcer scars. Mostly the tumor does not disappear completely, but a node of scar tissue remains in its place. With incomplete recovery, the tumor decreases only to a certain limit and after some time begins to grow again. Microscopically, in the cancer cell after irradiation with x-rays, degenerative changes leading to cell death are found: the cell nuclei become bubble-like and are unevenly stained; subsequently, pyknosis occurs and the nucleus disintegrates into small pieces. The protoplasm swells and vacuoles appear in it; the boundaries of the cells merge. Signs of nuclear division completely disappear. Subsequently, the almost unstaining parts of the cells remain, consisting of remnants of protoplasm and nuclear clumps. Spaces form between the cells, into which connective tissue penetrates. Among the degenerated cells, phagocytes appear that devour the remnants of cells. Large cells also form, filling the existing voids. When treating a malignant tumor, it is necessary to find such a dose that would destroy the tumor cell without damaging the tissues surrounding the tumor and without having a harmful effect on the entire body. In cancer, this dose is approximately equal to 90-120% HED (500-650 g), in sarcoma—60-70% HED (330-390 g). It is achieved either by cross-illumination of several fields with a deep tumor location or by increasing the distance between the tube focus and the skin with a superficial tumor location. Based on a large number of observations, it is known that the size of the dose used plays a huge role in the treatment of malignant tumors with x-rays, but the question of the extent of treatment duration is no less important, i.e., whether the dose is given in one session or fractionated over several days. The method of Wintz and Seitz, which prescribed the application of the entire dose in one day, often required patients to remain under the apparatus for 8-10 hours, which led to a sharp weakening of the patient, sometimes with a fatal outcome. Unsatisfactory results from treatment and frequent complications forced many authors (Freund, Schwarz, Opitz, Fraenkel, Heimann, etc.) already in the first years after the appearance of the works of Wintz and Seitz to strive to change their methods. Kuttar scientifically and systematically developed the dosing technique. He proved that when treating cancer patients with x-rays, the outcome of treatment depends on the following factors: 1) the size of the given dose—2-3 thousand r are given per field; 2) the size of the dose given per unit of time—the dose is brought to 150-180 r per hour; 3) the duration of the treatment period. With this method—prolonged-fractionated—the skin can safely withstand up to 3,000-4,000 r per field without the danger of deep burns; 4) the quality of the filter: copper or zinc filters 2 mm thick are used. The resulting reaction—epidermicite—is stronger than from HED, but it completely passes, leaving only pigmentation behind. Kuttar had very good results with this method of radiotherapy in treating cancer of the larynx, nasopharynx, uterus, etc., with observation periods up to ten years. Many German and American authors also report favorable impressions from the direct effect of Kuttar's method on cancer of various organs. In the Institute for the Treatment of Tumors (Moscow), a modified Kuttar method was applied to three hundred cancer patients (Freund, Domshlak). The immediate result is good.—In view of the fact that Kuttar's method requires a large number of long sessions—a factor economically burdensome—attempts are being made to modify this method. Experiments in this regard to date have been unsuccessful, as it remains insufficiently clarified which of the elements of Kuttar's method—the size of the dose given to the skin, fractionation, or duration—is the most important; it is also possible that each plays an equal role and none of them can be changed or discarded in treatment. The American author Pfahler published another method of fractionated treatment, the so-called 'saturation method.' He proceeds from the following considerations: if 100% HED is applied to the tumor, then the biological effect of the rays slowly decreases according to a certain curve: after 14 days only 50% of the original dose remains, after 30 days—20%, etc. Pfahler believes that for the success of treatment, the missing amount up to 100% should be added daily. With such saturation, in his opinion, those cells that were not affected in the first session are gradually destroyed. The danger of this method lies in the possibility of delayed harmful effects from the repeated application of x-rays, especially the harmful effect on the vessels. Therefore, it is recommended to give no more than 200% HED per field.—The problem of dosing has not yet been fully resolved in individual details, but it is already clear that the classical HED as the limit of skin tolerance to x-rays and the cancer dose in its original definition by Wintz and Seitz have lost their significance, and further successes can only be expected from a more in-depth development of the technique of fractionated treatment in the broad sense of the word. When using R. after each complete series of sessions, a long break in treatment is necessary so that the patient's body can recover. Re-treatment with the methods of Wintz and Seitz is permissible no earlier than 8-12 weeks after the end of the first series; with fractionated treatment—no earlier than 12-16 weeks. Re-treatment is useless if the tumor turned out to be radioresistant, i.e., did not respond to treatment. R. is also used as an additional method of treatment in operations for radical removal of the tumor to improve the treatment outcome—reducing the number of recurrences and metastases. R. is used before and after surgery. For preventive treatment, doses are used that are significantly smaller than the one capable of destroying the tumor. Preventive treatment of patients with cancer of the breast worsened the results of the operation. For cancer of the breast, no more than 50% HED is given per field. For cancer of the uterus, up to 100% can be given. For preoperative treatment, very large doses should also not be used, as such a technique can lead to a delay in healing of surgical wounds.—R. in inoperable cases of cancer can lead to their transformation into operable ones. In the Institute for the Treatment of Tumors (Freund, Domshlak), such a result of fractionated treatment was obtained in twenty cases of cancer of the breast.—Cancer of the skin is a very favorable object for R. The outcome depends on the histological structure of the tumor and on how deeply the skin is affected. The best results are obtained with the basal form and superficial cancer. The experience of many clinics has shown that for cancer of the skin, both hard rays with a heavy filter and soft rays without filters (Coste) can be used. The dose varies from 100% to 200-250% (Miescher). The percentage of cures with observation for 1-5 years—from 60% to 97%. The type and characteristics of the base of the tumor and the condition of the tissues surrounding the tumor play no small role in the result of R. The spread of the tumor to bone and cartilage, the presence of scar tissue and calluses around the tumor significantly worsen the prognosis. Often after a favorable outcome, recurrences appear, which are not sufficiently sensitive to rays upon repeated treatment. Cancers of the oral cavity and tongue are the most refractory tumors in relation to x-rays. Satisfactory results are obtained with curietherapy. R. can be used as a palliative to reduce pain or as an additional method after or before surgery for irradiation of regional glands.

For cancer of the nasopharynx, very good results have been obtained with fractionated treatment according to the Coutard method, which in 46 cases of cancer of the tonsils had a 26% recovery rate. Berwen prefers curietherapy or combined treatment with X-rays and radium. Undoubtedly, sarcomas of the pharyngeal ring and lymphoepitheliomas in this area respond well to radiotherapy. The best object for radiotherapy is cancer of the larynx. The Coutard technique gives very good results here. Severe complications are possible in the form of acute edemas requiring emergency tracheotomy and necrosis of the cartilage. Cancer of the digestive tract. Radiotherapy for cancer of the esophagus in the sense of final cure is useless; it should be considered as a palliative, which often gives temporary relief to the patient--improvement in swallowing due to the breakdown of the tumor. Radiotherapy is contraindicated in all cases where there is cachexia or metastasis of the tumor to internal organs. Combined radiotherapy and radiotherapy is recommended, carried out with great caution. In the medullary form of cancer, rapid breakdown of the tumor with subsequent perforation is possible. For cancer and sarcoma of the stomach, radiotherapy does not give favorable results. Most authors believe that in all cases of stomach cancer where surgery is possible, it is necessary to resort to the knife without delay. Due to the fact that when the stomach is irradiated with X-rays, other internal organs (kidneys, adrenal glands and pancreas) also fall into the irradiation field, radiotherapy is accompanied by complications that lead to rapid exhaustion of the patient and death. Finsterer and Werner proposed the following technique: to perform laparotomy, suture the stomach 65° into the surgical wound and after healing, irradiate the exposed stomach, but even this complex technique did not give satisfactory results. Gölffelder obtained complete recovery in three cases of stomach cancer from the fractionated method of treatment. Malignant tumors of the intestines do not respond to treatment with X-rays with the exception of sarcomas. A rather grateful object is cancers of the rectum, where it is often possible to prolong the patient's life for several years and free him from suffering. The condition for a good outcome is the creation of an artificial anus before the application of X-rays. Combined therapy is also not contraindicated: introduction of radium to the tumor and radiotherapy. 4-5 fields are given and for each field up to 100% HED or with the fractionated method up to 150% HED per field. Cancer of the breast in the first stage (Steinthal) is subject exclusively to surgery, because the result of radical surgical intervention equals 70-100% of long-term cure. The literature speaks of 16% recovery in this stage with radiotherapy, with the exception of one report by Vince, who in 21 cases of cancer of the breast had long-term cure in 20 cases. In the second stage, the result of surgery is significantly worse. Therefore, in this stage as well, as in the 3rd and 4th stages, it is better to use radiotherapy, in suitable cases in combination with radiotherapy. In some patients after treatment, inoperable cancer becomes accessible to surgery. With metastasis of the tumor to bones and mainly to the spine, radiotherapy is a good palliative means for reducing pain and temporary restoration of organ function. A great discussion was raised about the use of radiotherapy after surgery to prevent recurrences and metastases. Some authors, according to them, obtained worsening of surgical results in cases where they used radiotherapy in addition to surgery, but most authors hold opposite views, - the data from the clinic of Bier, obtained by his assistant Hintze on a large material observed over twenty years, are very convincing. Observations in the Institute for the Treatment of Tumors (Moscow) over ten years (Frenkel, Domshlak, Zabludovsky) confirm the fact of improvement in results from radical removal of the breast with preventive radiotherapy (after surgery). The condition for a favorable effect of this method is the use of low doses: for each field no more than 50% HED (300 g). Treatment continues for 2 years--every 2-4 months one series of sessions; the supraclavicular, axillary glands and the operative field are irradiated. Radiotherapy is used with satisfactory temporary success in inoperable cases in cancer of a number of other organs--cancer of the prostate, testicles, penis. Better results in malignant struma. A special, very grateful area for the application of radiation therapy is cancer of the female genital sphere. Recently, most authors use combined therapy with X-rays and radium or exclusively radium. The result depends on the stage of the disease in which the patient is, the histological structure of the tumor and the general condition of the patient. According to world statistics, 35.6% of patients with uterine cancer are cured by surgery (remain five years without recurrence), 42.7% by radiation therapy. In the clinics of Berlin, Bonn, Kiel, 28% of all patients who sought help for uterine cancer were cured by radiation therapy. The results are much worse in cancer of the vagina. The question of surgery or combined radiation or exclusively radium therapy in cancer of the cervix or body of the uterus in the first stage remains open, but all patients outside the first stage of the disease are subject to radiotherapy and radiotherapy. In uterine cancer, radiotherapy is used with great success after surgery to improve the results of the operation. Sarcoma is more sensitive to X-rays than cancer, but complete and long-term recovery is obtained in a very limited number of cases. Among surgical diseases, radiotherapy is used very often in acute inflammatory processes. A dose of no more than 10-25% HED is given. Many authors have obtained very good results in almost 75% of all treated cases. Fried, Pordes, Heidenhein, Frenkel, Nisnevich, Zabludovsky applied radiotherapy in furuncles, lymphangitis, phlegmon, inflammation of the sweat glands, abscesses of soft tissues, etc. They also propose radiotherapy in tuberculosis of bones, joints and glands. Medium doses are given. Very good results are obtained in radiotherapy of actinomycosis.

* Radiotherapy in internal diseases. Among blood diseases, leukemia, both myeloid and lymphatic, is subject to radiotherapy (see Leukemia). Polycythemia gives satisfactory results, which are expressed in improvement of the general condition of patients, reduction of severe fatigue, which they usually complain of, and reduction in the number of red blood cells. The tubular bones are predominantly irradiated. The dose for each field is up to 450 g. The improvement lasts for several months. With periodic irradiations, the patient's health can be maintained in a satisfactory state and his relative working capacity preserved. In radiotherapy of lymphogranulomatosis (see), it is sometimes possible to prolong the life of patients for several years with appropriate radiotherapy. Lymphosarcoma, which stands on the border between blood diseases and tumors, is more sensitive to X-rays. The tumor sometimes disappears from small doses--20-25% HED. Goltsknecht in lymphosarcoma advises to perform a trial irradiation with a small dose in order not to cause radiotherapy cachexia due to the rapid breakdown of the tumor. Depending on the reaction, the dose is increased and repeated treatment is performed or it is stopped altogether. The results are somewhat better than in lymphogranulomatosis. Diseases of the endocrine glands. Among diseases of the thyroid gland, Basedow's disease is most suitable for radiotherapy. The high sensitivity of the thyroid gland in Basedow's disease to X-rays is connected with the increased functional activity of its cells in this disease. Therefore, great caution is required in dosing. The doses are no more than 20-30% HED per field. It is best to perform a trial irradiation and depending on the nature of the reaction, to perform a repeated session. The clinical course of Basedow's disease under the influence of irradiation is expressed as follows: after the first sessions, general nervous phenomena disappear--depressed mood, increased irritability, anxiety, sensation of fear, insomnia. Soon a decrease in tachycardia occurs, vomiting, diarrhea, sweating disappear. The patient gains weight and the basal metabolism returns to normal. Statistics of many large clinics prove the success of the application of radiotherapy in Basedow's disease. Sielmann in 500 cases had complete recovery in 50.5%, improvement in 44.5% and no success in 5%.-For tumors of the pituitary gland, radiotherapy is the only method that gives satisfactory results. Clinically, improvement is expressed primarily in a decrease in symptoms of visual disturbance, disappearance of headaches, dizziness and weakness. Cases of persistent long-term cure are described. The outcome depends on the histological structure; adenomas react best. The dose is up to 75% HED per field; a total of 6 fields. Radiotherapy is used, besides the listed diseases, in a number of others, such as pneumonia, arthritis, acute anurias, tuberculosis of the lungs, hypertrophy of the prostate, eye diseases, etc. The technique and dosage in these pathological processes are not sufficiently developed, and since there are many other means for their treatment, radiotherapy has not been given sufficient attention. (On the protection of the labor of X-ray personnel--see Radiotechnics.)