Roger A. Harvey

Some Physical Aspects of Electron Beam Therapy

The physical development of the high-energy electron beam has progressed sufficiently to permit investigation of its action on animals and more recently the initiation of human therapy. The present report is concerned with aspects of this physical development of the electron beam. The long-used therapeutic action of x-rays on tissue is essentially effected through the interaction with the tissue molecules of the secondary electrons produced in the absorption of the x-rays. Accordingly, the direct action of electrons from beta-ray sources has long been exploited in therapy. Examples are the use of Ra D applicators, and of such isotopes as 53I131, 20Ca45, and 79Au198, whose therapeutic action is primarily due to beta emission. The primary differences to be expected in the action of x-rays and electrons are only quantitative, involving such factors as dose distribution, dosimetry, and the dependence of the biological action on specific ionization. At the time of his development of the betatron in 1940, Prof....

Changes in the Central Nervous System Following Irradiation with 23-mev X-Rays from the Betatron

During the past three years, studies have been in progress to determine and analyze the effects of x-rays on the normal brain of the monkey and on tumors of the central nervous system of man. Although these studies have been carried out primarily with 23-mev x-rays, produced by the University of Illinois betatron, additional comparative studies utilizing 200 and 400 kv. x-rays have also been undertaken. Our findings, to date, would indicate that the brain of both monkey and man is more radioresponsive than previously supposed, and that the pathological changes produced by these radiations are due to a direct effect upon the neural elements. These observations are definitely contradictory to the observations made by previous investigators (1–5) who have irradiated the central nervous system of a variety of animal species, including man (6). In general, these authors have concluded (a) that the central nervous system is highly radioresistant, in that it requires many thousands of roentgens to produce any re...

Intolerance of the primate brainstem and hypothalamus to conventional and high energy radiations.

SHORTLY AFTER STUDIES of the effects of various radiations upon the central nervous system of monkey and man were begun in 1949, it was noted that the brainstem and hypothalamus were rather intolerant to large doses of x-rays from conventional x-ray equipment and to biologically equivalent doses of high energy x-rays from the A similar intolerance of these areas to equivalent dosages of high energy electrons has also been observed in studies of 17 mev (million electron volt) electrons from the betatron on the brains of monkeys.‘ This intolerance of the brainstem and hypothalamus of monkey and man to a variety of radiations becomes an important consideration in the planning of radiation therapy for patients with neoplasms of the central nervous system, particularly for those patients with neoplasms within or about the central axis of the brain. Both the brainstem and hypothalamus are quite radio-responsive. Radiation effects can be observed promptly after moderate dosages of irradiation and at prolonged intervals of time after irradiation, when delayed radiation damage may appear. Both the acute and delayed reactions may seriously alter the course of the patient’s life. The intolerance of the brainstem and hypothalamus to large doses of radiation appears to be due to two factors: l ) these areas subserve many functions essential for survival, and 2 ) these areas are much more radio-responsive than cortical areas. The much greater responsiveness of the brainstem and hypothalamus to irradiation will be demonstrated in this paper, and the clinical importance of these observations will be discussed.

Biological Effectiveness of High-Speed Electron Beam in Man

The electron beam from the medical betatron at this institution was successfully extracted in March 1950. It was reproducible in quality and quantity without difficulty for a variety of physical and animal experiments, and was first applied to man in March 1951, at energy levels up to slightly above 19 mev. The Siemens 6-mev betatron had been used previously by the Gottingen group (1, 5, 6, 8, 9) for extensive biological investigations and for therapy of superficial lesions, most of which were treated below the 6-mev rating of the machine. Since there is no essential physical difference between 6-mev and 20-mev electrons aside from depth of penetration, no marked difference in biological effectiveness or biological results was expected in our experience. The data from the lower-energy ranges could not, however, be transferred directly to our higher-energy ranges without a practical evaluation, because of the possible influence of different depth distributions and volume doses. Kepp (5) found the electron ...

Radiological Evidence of Growth in Children with Acute Leukemia Treated with Folic Acid Antagonists

The ability of folic acid antagonists to provide temporary bone marrow remissions in children with acute leukemia has been described by many investigators since the initial account by Farber and his co-workers (2). A clinical report from this laboratory by Poncher et al. (4) provided corroborative evidence that antagonists were able to prolong life and that temporary bone marrow remissions were accompanied by definite improvement in the osseous manifestations of the disease. The average duration of life in untreated acute leukemia patients was five and a half months and in the folic acid antagonist-treated group thirteen and a half months. This prolongation of life was shown to be statistically significant. Since the growth process appeared to be uninterrupted in spite of the long duration of the disease (more than two years in several cases), it seemed of interest to evaluate radiographic findings in 21 patients treated prior to the antagonist era, and in 43 patients to-whom antagonists were administered...

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...

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 f...

Preliminary Clinical Experience with the Betatron

The betatron is primarily a physics research tool and industrial x-ray machine. We are exploring its medical possibilities and realize that it will be a long-term project. The present report high-lights some of our progress, some of the obstacles encountered, and some of the early biological effects we have observed. As its name implies, the betatron is an agency for producing high-energy electrons, i.e., beta particles. The desirability of great acceleration of electrons and the limitations of ordinary transformers for this purpose were recognized many years ago. As far back as 1922 the general idea of speeding electrons in a magnetic field was recognized as feasible. Since that time many university and industrial groups have tackled the problem, and in 1940 Kerst (1) succeeded in accelerating and guiding electrons into a useful beam of x-rays. At present we are converting these high-speed electrons into extremely powerful x-rays but, as Uhlmann and Skaggs (2) have shown, electrons can be brought out as ...

Comparison of biological effects of whole-body irradiation with 22.5-Mev x-rays, 18-Mev electrons, and 400-Kev x-rays in the rat.

Recently, two types of high-energy irradiations, 22.5-Mev peak X-rays and 18Mev electrons, have been available for biological use from the University of Illinois medical betatron. The availability of these high-energy radiations for therapeutic purposes has raised important questions as to whether there are any qualitative or quantitative differences between the biological effects of the high-energy radiations and the conventional lower-energy radiations. Quastler et al. (1-4) found that the highand low-energy X-rays acted on mice qualitatively in the same way. He also noted that there were quantitative differences in the effects of highand low-energy radiations on mice. Haas et al. (5) have shown that the efficiency (,) of 22.5-Mev peak X-radiation compared with 200-kev peak X-radiation was approximately 0.56 for erythema of rabbit skin and 0.67 for epilation of rabbit skin. The large differences in depth dose characteristics of the 22.5-Mev peak X-ray beam and the 18-Mev electron beam have been described (6, 7). With the 22.5Mev peak X-ray beam, the dose increases with increasing depth in the first few centimeters of tissue, the maximum depth dose occurring at about 4.5 cm. With the 18-Mev electron beam, no marked increase in dose occurs near the surface. The experiments reported here were planned to compare the effects of the highenergy betatron irradiations with those of lower-energy irradiations from a conventional 400-kev peak therapy machine under experimental conditions where the differences in depth dose distribution were eliminated. The main objective of these experiments was to ascertain whether any qualitative differences exist between the

Death from drug-induced hemolytic anemia

Fatal hemolytic anemia occurred in a 71-year-old man after trimethoprim-sulfamethoxazole was given for presumed cystitis. Administration of this combination has previously caused multiple hematologic reactions by affecting folic acid metabolism. Megaloblastic anemia and neutropenia have been produced by both of these agents, while sulfamethoxazole alone has induced acute hemolytic anemia in patients with hereditary deficiency of glucose-6-phosphate dehydrogenase. Although hematologic complications of trimethoprim-sulfamethoxazole treatment usually follow long-term or high-dose therapy, acute reactions apparently may occur at lower doses as well.