Betatron X-ray Research Articles

Five-year results of betatron x-ray therapy.

From March, 1949, until May, 1953, 114 patients suffering from advanced malignant disease were treated on the betatron at the University of Saskatchewan, using X rays of an energy of 22 or 23 MeV. This paper is written in an attempt to evaluate the late results of this treatment, from a purely curative point of view, rather than taking into account temporary palliation achieved, since consideration of the latter is unlikely to be purely objective. The betatron at the University of Saskatchewan is situated in a special building behind the Physics Department and details of the housing may be found elsewhere (Harrington, Haslam, Johns and Katz, 1949). The instrument produces X rays through a fixed horizontal field and, by the insertion of lead moulds, fields of any size from 0 to 15 × 15 cm at 105 cm F.S.D. can be provided (Johns, Darby, Watson and Burkell, 1950). By means of a special filter the beam is flattened so that, by a combination of fields, a very homogeneous distribution of radiation can be obtain...

The possibilities of betatron treatment in carcinoma of the paranasal sinuses and of the larynx.

My role in joining the symposium is to discuss in general the possibilities of betatron therapy in cancers of the nose-and-throat area and its relation to conventional x-rays, and to present a few irradiated cases. The main question is what is the sense of using megavoltage radiations in lesions which are close to the surface and to which conventional x-ray may also deliver an adequate, high tumor dose. The betatron may produce two types of radiation: high-energy x-ray beam and highenergy electron beam. Their depth dose distributions, and accordingly their indications, are entirely different. Figure 1 shows the differences in depth dose distribution. In the curve of conventional 400 kvp the maximal dose is at the surface and the decrease is fast, so that at 10 cm. depth the dose is less than 40% of the maximum. In the curve for the 23 mev betatron x-ray beam, the dose is

PHOTONEUTRON EMISSION FROM Th232, U233, U238, AND Pu239

Measurements have been made of the numbers of neutrons emitted by the fissile materials Th232, U233, U238, and Pu239 under irradiation by betatron X-rays of various energies up to 23 Mev. Yield curves and corresponding cross section curves are given for these nuclides. At low X-ray energies it is found that the yield curves differ from those found with non-fissile heavy elements, corresponding to the fact that even at zero X-ray energy the fissile materials suffer (spontaneous) fission.

Calculations of Energy Dissipation Characteristics in Water for Various Radiations

The variations of chemical and biological yields with radiation quality provide important clues for elucidating reaction mechanisms. Before attempting a detailed interpretation of such variations we require (1) a knowledge of the amounts of energy dissipated in the system by the different types of particle over their various kinetic energy ranges (in other words, the spectrum of energy dissipation versus kinetic energy for each type of particle), and (2) a model of the way in which energy is dissipated along the tracks of particles with particular emphasis on linear energy transfer. Both requirements involve the application of stopping-power formulas and are therefore not entirely independent of each other; however, they are to some extent separable, and this paper is concerned with the first aspect. At the 1955 International Conference of Radiobiology, calculations were given of certain energy-dissipation characteristics in water of 200-kvp total X-, 220-kvp primary X-, Co60 y-, and 25-Mvp betatron X-rays (1). Results were presented in terms of the relative amounts of local energy (QT AT) dissipated by electrons in kinetic energy ranges covering the complete spectrum. Local was taken to include all collisional energy transfers (excitation and ionization) up to 100 ev. Deltatracks or secondaries produced with an energy greater than 100 ev were treated separately, that is, as being distinct from the parent track. Mean linear energy transfer values were also calculated according to the following definition:

The effects of conventional and high-energy x-rays and electrons in fractionated dosage on rats.

The use of very high-energy gamma and electron radiation for the treatment of cancer in man poses the question of the eventual biological effects on the tissues involved. Does radiation of such type cause a different response qualitatively and/or quantitatively in comparison to standard x-ray exposure? Investigation of this problem is a prerequisite to the application of high-energy radiation therapy. Though many studies have been conducted (1–6), research is continued in the interest of improving treatment technic and enhancing the response of the malignant tissues to radiation. Biological effectiveness has been observed to vary with the energy of the irradiating agent (7–9, and others). Quastler (5), Haas (1), and others have demonstrated such variation in biological objects irradiated with betatron x-rays of 22 MEV and electrons of similar energy. The difference of the effects as compared with those of 400- and 200-kv x-ray exposures seems to be of an entirely quantitative nature; no qualitative changes could be detected.2 The purpose of the experiments to be recorded here was to establish the degree to which fractionated x-ray and electron dosages influence the survival and other biological activities of rats in comparison to equal amounts of ionizing radiation of lower energy. Methods For these experiments, male albino rats of the Holtzman strain were used. A two-week period was allowed for conditioning the animals to their new environment before the first irradiation took place. The rats were sorted at random into several groups, each consisting of 22 animals. One group was used for exposure to 400-kv x-rays generated by a General Electric 400-kv unit (h.v.l., 2.1 mm. Cu). A second group was irradiated by a 22-MEV betatron x-ray source (h.v.l., 14 mm. Pb), while a third received electron radiation of 20 MEV energy.3 A final group was kept as a control but, except for exposure to radiation, was handled exactly as were the other animals. From each group 11 rats were treated simultaneously in a rotating Lucite cage, described elsewhere (11). This allowed more uniform irradiation and reduced errors due to individual dosage variations to a minimum. It also resulted in a saving of time since the wheel was placed at such a distance from the radiation source that only 6 r/min. were delivered to the animals. In this location the entire rotating cage (1 rpm) was uniformly covered by the 400-kv and 22-MEV x-ray beams. For electron beam irradiation, only sectional areas of the wheel could be irradiated. The electron beam was defined by a Lucite and brass shield having an opening identical in configuration with each of the twelve individual compartments in the Lucite wheel.

Studies of Dose Distributions in Water for Betatron X-Rays up to 37 Mev

A knowledge of the amount of energy dissipated at each location in a medium is necessary for an understanding of the diffusion of X-rays in the medium. The energy imparted to a unit mass of a medium is called the absorbed dose and is measured in ergs per gram. Since this quantity is difficult to measure directly, the customary procedure has been to use a detector, whose response is considered proportional to the dose, for determining the dose distribution. It is then necessary to perform an auxiliary experiment to determine the factor that would convert the relative values into absolute measurements of dose. Such measurements of highenergy X-rays are described in this paper. Many investigators have made relative dose-distribution measurements at high X-ray energies in low-atomic-number materials like water and masonite using ionization chambers and photographic film as detectors. Surveys of such work may be found in various papers and publications including those of Johns (1), Laughlin (2), Mayneord (3), and Marinelli (4). More recently anthracene crystal dose measurements in water and comparisons with ionization measurements for high-energy X-rays have been made by Robson and Gregg (5). The interpretation of many of these results required the use of an infinitely broad X-ray beam. Beams of small diameter were used in practice, and hence the interpretations are not completely valid. The effect of smallversus large-diameter beams has been measured for 35and 90-Mev peak energy X-rays (6, 7). It is possible to convert relative dose measurements made with ionization detectors into absolute dose measurements by calculating the conversion by the Bragg-Gray relation (8-12). This relation is usually written as

The Relative Biological Effectiveness of 180-Kevp and 22.5-Mevp X-Rays Determined from the Dose-Survival Curve of Saccharomyces cerevisiae

The use of supervoltage X-rays for deep therapy has stimulated interest in the relative biological effectiveness (RBE) of such radiation compared to that conventionally employed (200 to 400 kevp). For betatron X-rays of about 20to 31Mev peak energy, reported RBE values have ranged from 0.4 to 1.0 (1-7); for betatron electron beams of about 3 to 6 Mev, from 0.4 to 1.45 (8). Although this range of values may be due to differences inherent in the nature of biological systems, it may also stem, at least in part, from the limited precision of the methods employed and from differences in the basic concepts underlying the dosimetry, e.g., air (roentgens), tissue dose, and absorbed dose (rads). We have defined the RBE of supervoltage X-rays as the ratio of absorbed dose of standard X-rays (180 kevp) to that of supervoltage X-rays (22.5 Mevp) when both produce the same biological effect. In the present experiments, employing the X-ray beams of the 180-kvp machine and the 22.5-Mev betatron at the SloanKettering Institute, the biological effect was measured in terms of the dose-survival curve of a microorganism. The technical problems involved in the determination

Modifications of Depth Dose Curves of High Energy X-Ray and Electron Beams by Interposed Bone

To determine by physical measurements whether interposed bone affects the standard depth dose curve of high-energy x-ray and electron beams, uniform bone plates of 0.5 and 1.0 cm. thickness were prepared by hydraulic compression of bone powder to the density of living bone and were suspended in thin plastic sheets in a water phantom. A ratio recording system was used to compare the dose rate in a stationary monitoring chamber with that of a small ionization chamber which was moved through the water phantom in step with the recorder chart motion. The chamber dimension prevented measurements closer than 0.5 cm. from the phantom surface or bone. The overall accuracy of the curves is estimated, from the close agreement of repeated measurements, to be better than 2 per cent. Figure 1 shows the comparative curves for 22.5 Mev betatron x-rays with 0, 0.5, and 1.0 cm. bone at the front of the phantom. A significant increase in dose rate and acceleration was observed in the build-up layer, with a maximum at about 3 cm. depth instead of the usual 4.0 cm. At depths beyond the build-up area the difference was insignificant, less than our 2 per cent estimated accuracy. Figure 2 shows the effect of 1.0 cm. bone interposed at depths beyond the build-up layer. Insignificant back-scattering and a pronounced dose increase up to 2 cm. beyond the bone were observed. These effects might be explained by the greater density and higher average atomic number of bone as compared with water. The curves for 13.1- and 17.8-Mev electron beams (Figs. 3 and 4) show that the range of penetration of both was shortened approximately 3 mm. by 0.5 cm., and 6 mm. by 1.0 cm. bone. A moderately increased build-up area also was seen after passage through bone. The shortened penetration is presumably due to higher Coulomb scattering cross section, and the increased build-up layer to increased x-ray production by the heavier bone. These modifications of the depth dose curves of high-energy radiations by interposed bone may explain some of our unsatisfactory results and unexpected skin and mucosal reactions and should be considered in treatment planning to deliver a maximal tumor dose in the presence of interposed bone.

Contaminant Dose from Incident Neutrons Associated with 22.5-Mev X-Rays from a Betatron

The flux of thermal and fast neutrons present at the patient treatment position has been determined by measurements of the activity induced in rhodium foils and in sulfur. A previously published energy spectrum of fast neutrons produced by photodisintegration reactions with 22 Mev Bremsstrahlung in heavy elements has been used in evaluating the activation information. There are 9 × 105 fast neutrons/cm.2 and 9 × 103 thermal neutrons per roentgen in the center of the collimated and compensated betatron x-ray beam at a treatment distance of 80 cm, from the target. The fast neutron spectrum has a peak intensity at 0.8 Mev. The dose produced by thermal neutrons is completely negligible. A calculation of the fast neutron dose induced in tissue has been carried out for two typical irradiation conditions: (1) four-port irradiation of the trunk; (2) bilateral irradiation of head.

The relative biologic effects of x-rays and beta rays.

Investigations of the biologic effects of different types of ionizing radiations suggest that quantitative differences in response occur even though identical amounts of energy are absorbed per unit volume of tissue. Since the development of technics for the treatment of cancer and other diseases with radioactive isotopes, information regarding the relative biologic efficiency of the emitted beta particles and x-rays is required to utilize properly the knowledge that has been acquired by experience with x-rays. We, as well as others (9), have been impressed with the striking tolerance of normal tissue for beta irradiation. The dosage that may be given without producing necrosis or other serious reactions seems to be many times greater for beta rays than for 200-kv x-rays. Most of the data in the literature regarding relative biologic efficiency deal with alpha rays, neutrons, gamma rays, and supervoltage x-rays. Among the reports comparing beta rays and x-rays there is a lack of uniformity in results obtained. Stapleton and Zirkle (15) compared the efficiency of beta rays from P32 with the gamma emission from Ta181 in inhibiting the hatching of Drosophila ova and found no significant difference. Using the same material, Zirkle (17) compared 200-kv x-rays and P32 beta rays and found the latter to be less efficient by a factor of 0.64. Snyder and Kisieleski (13), studying the twenty-day LD 50 dose in mice for the beta emission of Na24 and 200-kv x-rays, reported a ratio of 0.7. Evans and Quimby (4), using Na24 beta rays and 200-kv x-rays to produce lymphopenia in mice, reported the former to be less efficient, the ratio of beta to x-rays having the value 0.66. Taking the graying of hair in mice as a biological end point, Austin et al. (1) compared 17 Mev electrons with 100-kv x-rays and found a ratio of 0.6. Gartner (6) compared the effects of fast electrons from a 6-Mev betatron and 90-kv x-rays on cultures of chicken heart fibroblasts and demonstrated a relative electron efficiency of 0.51. Friedell et al. (5) reported comparable skin reactions following physically equivalent doses from Sr90, RaD and E, and Ru106, and stated that these reactions approximated the skin effects produced by a 44-kv Philips contact unit. Wirth and Raper (16) found the threshold erythema dose on human skin for P32 to be 813 rep, while Low-Beer (11) estimated that a dose of 143 rep from P32 produced a similar reaction. Crabtree and Gray (3) found no quantitative differences between beta, gamma, and roentgen rays in efficiency for inhibition of anaerobic glycolysis in the rat retina. We are presenting a preliminary report of our study of the relative biologic effects of medium voltage (120 and 200 kv) x-rays and beta rays emitted by P32.

Photodisintegration of the Deuteron by 95-Mev Bremsstrahlung

Photoprotons produced by irradiating deuterium gas with betatron x-rays have been detected with stacks of unsupported Ilford emulsions. The differential cross section was determined for photon energies between 20 and 65 Mev and for seven angles of proton emission. The observed angular distributions are well fitted by $f(\ensuremath{\theta})=(\ensuremath{\alpha}+{sin}^{2}\ensuremath{\theta})(1+2\ensuremath{\beta}cos\ensuremath{\theta})$. The experimental results for angular distribution and total cross section have been compared with theoretical predictions assuming a purely central force. Striking departures from the central force theory are observed as the photon energy increases from 20 Mev.

Spatial Distribution of Energy Dissipation by High-Energy X-Rays

The space distribution of energy dissipated by betatron x-rays results from the combined propagation of the x-rays and of their secondary electrons. This distribution has been calculated for a 40-Mev bremsstrahlung spectrum incident on a mass of water. The calculation is described and the results are compared with related experiments.

BETATRON IRRADIATION OF AQUEOUS GERIC SULPHATE SOLUTION

Ceric ions, from ceric ammonium sulphate dissolved in aerated 0.8 N sulphuric acid solution, are reduced by Co60 γ-rays and betatron X-rays of 23 Mev. peak energy. G values were calculated on the basis of calculated electron distributions.

Photoprotons fromMo100andMo92

The absolute yield and the energy and angular distributions of protons emitted from targets of concentrated isotopes ${\mathrm{Mo}}^{92}$ and ${\mathrm{Mo}}^{100}$, under betatron x-ray radiation of maximum energy 22.5 Mev, have been determined with nuclear emulsions as detector of protons.For ${\mathrm{Mo}}^{92}$ the proton is less tightly bound than the neutron by 5.0 Mev; for ${\mathrm{Mo}}^{100}$ the proton is more tightly bound by 2.4 Mev. Comparison of the large yield and the energy distribution of protons from ${\mathrm{Mo}}^{92}$ with those calculated from the statistical model shows good agreement except for an observed excess of high energy protons, which are also anisotropic. They are presumably due to a direct emission process with which neutron emission does not compete in the normal way.With ${\mathrm{Mo}}^{100}$, however, the yield, though 20 times smaller, exceeds the yield predicted on the statistical model by 20 to 125 times depending upon the processes and parameters assumed in the calculation. Most of the protons, therefore, must come from a direct process. The observed energy distribution is similar to one computed using the experimental ($\ensuremath{\gamma}, p$) cross section if it is assumed that the residual nucleus is left with a typical exponential energy level density distribution. The angular distribution is strongly anisotropic with a maximum near 45\ifmmode^\circ\else\textdegree\fi{}, for protons of energy greater than 5 Mev.

BETATRON IRRADIATION OF WATER SATURATED WITH BENZENE

The oxidation of benzene to phenol in dilute aqueous solution by Co60 gamma rays and betatron X-rays (23 Mev. peak energy) is compared with the oxidationof Fe++ to Fe+++ under similar conditions. The ratio [Formula: see text]was the same for Co60 and betatron radiations. The yield for the Co60 radiations was about 10% greater than the apparent yield for the betatron radiations, the difference probably being attributable to dose determination at high energies (>1 Mev.). It is concluded that both reactions are independent of energy and dose rate over the ranges investigated.

Comparison of dose distributions in patients treated with x-ray beams of widely different energies.

All of the work published to date on supervoltage roentgen therapy indicates a lack of specific cancericidal advantage in relation to wave length of the radiation. The chief advantage of super-voltage therapy is an increase in quantity of radiation delivered to a deeply situated tumor. Normal tissues unavoidably irradiated have shown some rather slight arbitrary differences in tolerance to higher-energy radiations. These differences may well be related to difficulties in physical dosage measurements of absorption of qualities so closely related as those produced at 200,000 volts, 400,000 volts, and 1,000,000 volts. The 23,000,000-volt betatron has given us an opportunity to evaluate differences in dosage effects over a much greater range of voltage than hitherto available. The purpose of this presentation is to compare the dosage distribution of x-rays from a 400,000-volt x-ray machine with those from a 23,000,000-volt betatron. There are a minimum of five differences in the absorption of the radiations from these two sources which should be emphasized at the start. These are as follows: 1. The maximum dose for 400-kv. x-rays with a half-value layer of 2.75 mm. Cu is approximately at the surface, while with the betatron it is slightly over 4 cm. within the body (1, 4). 2. The relative dose for 400-kv. x-rays is 37 per cent at 10 cm. and 10 per cent at 20 cm.; with the betatron it is 81 per cent at 10 cm. and 54 per cent at 20 cm., both with 10-cm. ports (1,4). 3. Side scatter is important for 400-kv.p. x-rays, but for the betatron x-rays scatter is predominantly forward (1,4). 4. The entrance skin dose is at the peak with 400-kv. x-rays and at approximately 35 per cent of the peak dose with the betatron. The exit skin dose is usually negligible with 400-kv. x-rays, while with the betatron it may be higher than the entrance skin dose (1). 5. Relative absorption of the radiations is high in bone and low in fat at lower voltages; it is more nearly equal with the betatron (3, 6). For practical purposes we have selected 5 patients treated with the betatron and have compared their actual dose distributions with those which might have resulted from the use of the lower-energy machine. These patients had tumors located in different parts of the body and in both central and eccentric position. Treatment planning was conducted in a routine fashion and without thought or reference to competing methods, with the exception of one chest case for purposes of demonstration. The number of fields of treatment differ with the two technics, simply because the 23-mev x-rays have so much greater range that one has an almost unlimited number of approaches to a lesion. The number of treatments, size of daily treatments, rate of dosage administration, and over-all treatment period in terms of weeks are not significantly different between the two methods.

Betatron cancer therapy.

In the last few years we have all witnessed with varying degrees of interest a tremendous increase in the upper limits of supravoltage energies for possible therapeutic application. A variety of radiations have become available, some in adequate quantity for the first time. We have been using a 24,000,000-volt betatron which yields a very powerful beam of x-rays and a less well developed external beam of electrons (3, 6). Most of our work in the last year and a half has been with the x-ray beam, although at present we are diverting some of our attention to engineering problems and animal tissue effects of the electron beam. The betatron x-ray beam offers some very appealing distribution advantages in tissue (4). In Figure 1 is shown the distribution of density in a film phantom with a 200-kv. beam path and with the 24,000,000-volt betatron x-ray beam path. In the latter the sparing effect on the superficial tissues at the site of entrance of the beam (on the left in the illustration), the concentration of density deeper along the path, the extreme degree of useful penetration, and the lack of significant scatter along the edges of the path are important. In contrast, the 200-kv. beam path shows no sparing effect at the site of entrance of the beam but rather a concentration of density at the surface and for a few centimeters forward, limited penetration, and considerable side scatter. This distribution of density should clearly indicate separate zones of usefulness for the different types of equipment, although the decreased skin reactions with the betatron may eventually increase its applicability even for subsurface lesions. With conventional x-ray therapy equipment, dosage is conveniently measured and understood in terms of the roentgen. We have also been using the roentgen unit for dosage measurement with the betatron but are fully aware of the need for a method of measuring dissipated energy in terms of ergs per gram of tissue. For this purpose, we are investigating sensitive calorimetric methods of making a fundamental measurement of the actual energy dissipated by the x-ray beam. We use a 25-r Victoreen thimble chamber inserted in an 8-cm. cube of lucite. In the middle of this cube, the chamber is at the maximum or peak of the depth dose intensity. Our dose rate under these conditions, and with complete collimation and filtration of the beam, is usually around 100 r per minute at 84 em. from the target of the tube. The dose rate is about doubled without filtration. Biological investigations on relative effectiveness of the betatron roentgen by Quastler (5) and more recently by us (1, 2, 4) have shown that greater quantities of measured roentgens are required from the betatron than from machines of lower voltage to produce equal tissue effects. Unfortunately this of therapy, or have widespread terminal cancer.

Calorimetric Determination of the Energy Flux of 22.5-Mev X-Rays

A sensitive method of calorimetrically measuring the energy flux of an x-ray beam is described. Thermistors are employed as the temperature-sensitive elements and are embedded in the irradiated material in a calorimeter. Details and results of the application of this technique to a betatron x-ray beam are described. This method can be applied to x-ray beams of other energies and does not require high intensities.

Cross Sections for the Photo-Disintegration of Nitrogen and Oxygen Nuclei by 100-Mev Betatron X-Rays

Nuclear disintegrations caused by x-rays from the 100-Mev betatron have been investigated with a cloud chamber. The disintegrations studied are those occuring in tbe filling gas of the cloud chamber; they are observed as single, double (flag), and multiple (star) tracks. The singles are nuclear recoils mostly from (gamma,n) processes; according to the authors preliminary analysis most of the flags in nitrogen result from (gamma,pn) reactions; the stars represent various modes of disintegration involving the emission of several charged particles and probably neutrons. Approximate values of the integrated cross sections have been obtained for the flags in air, and for singles, flags, and stars in nitrogen and oxygen, for a peak betatron energy of 100 Mev. The latter measurements give the total integrated photo-disintegration cross sections for nitrogen and oxygen.