In the Treatment of Cancer* Radioactive Isotopes and Nuclear Radiations

Radioactive Isotopes and Nuclear Radiations in the Treatment of Cancer*

JOHN H. LAWRENCE AND CORNELIUS A. T0BIAs

(Donner Laboratory and Donner Pavilion, University of California, Berkeley, Calif.)

It is now @20years since we began to use arti shipments is for medical use, and one-third of ficially produced radioactive isotopes in cancer re these shipments are for cancer therapy. For in search and in medical research. Actually, our first stance, there are 50 medical groups in the United therapeutic trials were in 1936. In the early days States using radioactive colloidal gold and radio the hope was that at the end of @0years one could active colloidal chromic phosphate for interstitial report outstanding examples of selective localiza infiltration in various types of cancer, such as tion of radioactive compounds in neoplastic tissue, prostatic, uterine, and bronchogenic. Two hundred making it possible to give the tumor tissue many fifty groups are using radioactive gold, chromic times more irradiation than the surrounding, nor phosphate, and yttrium colloids in the treatment mal tissues. of cancer metastasized to the pleural and perito Up to the present moment, investigations with neal cavities. There are 400 groups using iodine only two radioactive isotopes have given us impor 181 in the diagnosis and treatment of hyperplastic tant therapeutic applications in hyperplastic and and neoplastic thyroid disease and 889 groups neoplastic diseases through selective localization. using @32forthe treatment of polycythemia vera These are radiophosphorus in the treatment of and chronic leukemia. During 1954 there were polycythemia vera and radioiodine in the treat over 5,000 shipments of radioactive iodine from ment of the thyroid hyperplasia of Grave's disease Oak Ridge to individual users, over @,500ship and in the palliative treatment of certain thyroid Inents of radioactive phosphorus, and 6@ ship cancers. However, one who has worked in the field ments of radioactive gold. At the present time from the beginning and who is asked to sum up his there are 30 cobalt teletherapy units in the United experiences can't help saying that the therapeutic States in use for external irradiation therapy of achievements have been disappointing; but even cancer with high energy gamma rays, and 50 more in the early days we believed that the greatest are being planned (1).' contribution of radioactive isotopes in the field Most of the isotopes which have been used in of medical and cancer research would lie in tracer the therapy of hyperplastic or neoplastic diseases applications, and we have devoted most of our in the form of internal, intracavitary, interstitial, energies to the latter. contact, tele, or fission radiation are listed in Even though the achievements in prolongation Chart 1 in the order of increasing atomic number. of life and cures in cancer have not been great so Early work by Kruger in this laboratory 15 far, one should not dismiss too lightly the con years ago (@5) and by Zahl at al. (59), followed by tributions of artificial radioactivity and nuclear the uranium fission experiments by Tobias at al. radiations in cancer therapy. The clinician should (55), more recently has led to the trial of boron-lO not underestimate the importance of relief from in the treatment of brain tumors, particularly glio pain and extension of comfortable life, and here blastomas, the radiation being derived from the their value is well established. fission of the boron nuclei after slow neutron cap The importance of the products of nuclear phys ture (7). Kruger bathed tumor slices in boric acid ics in cancer therapy is pointed up by the fact that solution in vitro and then irradiated them with demands for radioactive isotopes in medical and slow neutrons, causing fission of the boron nuclei biological research have risen rapidly in the past 10 into lithium and alpha particles. The ionization ob years. The shipments of radioactive isotopes from tained is relatively densely localized, the particles Oak Ridge National Laboratory have risen from traveling about one cell diameter (55). After borax less than 500 in 1946 to almost 1@,000 in 1954. containing boron-lO was injected intravenously Seventy per cent of the total dollar value of all into patients with brain tumors who were then ex posed to soft neutrons from the atomic pile, Farr, * Presented as part of the Symposium on Radioactive Iso topes and Cancer at the meeting of the American Association Sweet at al. (7, 13) have been able to deliver a few of Cancer Research in San Francisco, April 16, 1955. Papers â€˜Atthe International Conference @nthe Peaceful Uses of presented by David M. Greenberg and by Jacob Furth have Atomic Energy held in Geneva in August, 1955, the author appeared in the August, 1955, and the January, 1956, issues of learned from Professors Modestov and Fateyeva that there are Cancer Research, respectively. 150 such units now in operation in the Soviet Union. 185

hundred roentgens to the tumor tissue by such fis palliative treatment of advanced cancer of the sion energy, but this is probably insufficient to give bladder, but the survival time is not available for real therapeutic effect. Pathological studies of eight a large series of patients (58). The beta- and gam of the first ten patients treated at Brookhaven ma-emitting isotope Na24 has also been tried in the showed changes suggestive of irradiation effects in treatment of chronic leukemia, but the method has three patients; however, large areas of viable tu not found wide usage, since there is no selective mor were found in all cases (13). More recent in localization of sodium. vestigations by Kruger have shown that the con The first example of a successful application of a centration of boron in the boundary between nor radioactive isotope in therapy was the treatment mal and tumor tissue in glioblastoma multiforme of polycythemia vera with @32â€¢Enoughexperience tumors in mice can be increased by injection of has been gained over the past @20yearsto allow one

SOME OF THE THERAPEUTIC USES OF RADIOACTIVE ISOTOPES

Glioblastoma multiforme Bladder carcinoma Polycythemia, chronic leukemias, breast cancer Control of oscites and pleural effusion in metastatic Deritoneal and aleural carcinoma

.@ carcinoma, cervix carcinoma, bronchogenic carcinoma erkeratosis, basal cell carcinoma, squamous cell carcinoma â€˜iancarcinoma @ carcinoma, naso-pharynx tumor, maxillary tumor, I Iâ€¢.' esophaqeal carcinoma, uterine body carcinoma 1 1 carcinomaDeep-seatedcarcinoma, cervix carcinoma, bronchogenic â€”@Bladder tumors :...Prostate carcinomaOvarian carcinoma5r90Pterygium, vernal conjunctivitis, vascularization of cornea Hepatomegaly and splenomegaly in advanced leukemia

II â€” â€” Thyroid cancer angina pectoris congestive heart failure. hyperthyrodism Hepatomegaly and splenomegaly in advanced leukemia J 1 Control of ascites and pleural effusion in metastatic carcinoma I I Prostate carcinoma, cervix carcinoma, bronchogenic carcinoma Other isotopes used in therapy: Calcium, Chromium, Gallium, Arsenic, Thulium, Lanthanum, Ceseum, Astatine, Ruthenium

CHART 1 .â€”Some therapeutic applications of radioactive isotopes

Evans Blue dye containing boron-lO in the mole to say that the condition can be satisfactorily con cule (@6). Although the localization of the radio trolled by @82(@9).The survival of patients with isotope achieved by use of the dye is 30 times that polycythemia treated by @32isabout equal to that obtained after injection of boron-lO as borax solu in cases of pernicious anemia treated by liver or tion, the localization is greatest at the brain-tumor vitamin B@2and diabetes mellitus treated by in interface and is not uniformly distributed through sulin (Chart @),and is superior to any increased out the tumor tissue. Consequently, there is still survival rate yet achieved in such cancers as insufficient localization in tumor cells to provide breast or prostatic cancer with newer methods of the needed radiation. However, the use of such therapy (Chart 3). The median survival in pa boron-containing dyes should be explored. If fis tients with polycythemia vera is 14 years, com sionable material can be synthesized into com pared with a survival of approximately @0yearsfor pounds that will give great selective localization in an age-matched group of the general population. neoplastic tissue, there is little doubt that great Since 1936, when @32wasfirst used in the treat therapeutic benefit can result. ment of chronic leukemia (30), thousands of pa Sodium-@4 and bromine-8@ have been used in tients have been treated. As shown in Chart 3, the form of fluid instillation into the bladder for approximately 50 per cent of the patients with

Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 1956 American Association for Cancer Research. LAWRENCE AND ToBrJ1sâ€”Radioactive Isotopes in the Treatment of Cancer 187 chronic lymphatic leukemia treated by P@ will is pipetted onto it, and the plaque is then applied survive over 5 years (@8). This is somewhat better directly to the lesion. In the case of basal-cell car than the 8urvival in 1,600 cases treated by conven cinoma, a dose of 34,000â€”36,000 rep is delivered to tional methods reported in the literature review by the surface, and @0,000â€”@,500repdelivered to the Osgood (81). first millimeter depth in a period of 48 hours. This Between 1985 and 1940, in the early days of the method is producing results equal to those of any radioisotope work, we attempted to treat a group other of the more conventional methods now in use of patients with breast cancer and prostate cancer for the treatment of superficial skin cancer. metastatic to bone by means of intravenous or Radiophosphorus as colloidal chromic phos oral administration of @32orSr89 (@7, 80, 40). It phate (@1),first used by Jones et at. (fl), as well as had been demonstrated that strontium, like cal cium, localized to a high degree in bony tissue with less uptake than P@ in soft tissue. However, the results were not exciting, and this work was aban doned when it became evident that it would be impossible to deliver sufficient beta radiation to the bony lesions without causing severe marrow depression. Recently, Friedell (11) and others have re-introduced @32in this form of therapy and found again that there is some relief of pain and occasional evidence of healing. This type of ther apy may have a small place in the palliation of cancer metastatic to bone.

YEARS CHART3.â€”Survival in cancer, leukemia, and polycythemia compared with life expectancy in the general population (thin (0 z line). For polycythemia vera the dotted line represents the life >1 expectancy after conventional forms of therapy (56) and the -j thick black line shows our results after treatmentwith Pâ€•(@9). Iâ€”z For leukemia, the thick black line shows life expectancy in our LU patients with chronic lymphatic leukemia treated with Pâ€•(Q8) compared with average results in chronic myelogenous and LU 0@ lymphatic leukemia reported in the literature (dotted line) (37). For breast cancer the increased survival achieved with radical mastectomy (thick black line) over that following non radical procedures (dotted line) is shown (49). The survival rate in cancer of the prostate following the Huggins method of orchiectomy and diethylstilbesterol (thick black line) is corn pared with survival prior to Huggins' work (dotted line) (36). YEARS CHART Lâ€”The survival in polycythemia vera treated with colloidal radiogold (p2,14, @4)and radioyttrium, is @32compared with the survival in diabetes mellitus treated with insulin and pernicious anemia treated with liver and being currently given to patients suffering from vitamin B-1Q. pleural and ascitic effusions in metastatic car cinoma. This application of radioisotopes consti Friedell and associates have also made Sr9Â°ap tutes an important addition to palliative cancer plicators for use in the treatment of superficial therapy. Although there is no evidence that such tumors of the eyelids, conjunctiva, and cornea! therapy prolongs life, there is little question that it ulcers (1@). The treatment of skin cancer and hy relieves pain in many instances and slows down the perkeratoses by @32contacttherapy (31) has added accumulation of ascitic and pleural fluids, so that another successful method for the treatment of paracentesis is often unnecessary or need be done such lesions. Since 1943 Low-Beer has treated 350 at less frequent intervals. hyperkeratoses by this method with a 5-year eradi Colloidal chromic radiophosphate and radio cation rate of 98.8 per cent. Of the 190 basal-ce!! gold are also being used interstitially for the treat carcinomas treated, 97.6 per cent have been eradi ment of carcinoma of the prostate before distant cated for longer than 5 years. Also, 47 hemangio metastases develop (8, 9, 46). The beta radiation mas have been successfully treated by this meth from these colloids allows a large tumor dose of od. A small plaque of blotting paper is cut to fit the radiation to be given without damage to surround size of the lesion, the desired amount of Na2HP32O4 ing tissues, as might occur with conventional x-ray

therapy. Some workers point out the fact that good end results are reported (5, 34). In the chromic radiophosphate has an advantage over case of thyroid cancer, however, it is rare that radiogold in that the former emits only beta rays, radioiodine will localize sufficiently in a metastatic and less elaborate radiation protection measures lesion to give a good therapeutic result or cure, are needed. However, other workers believe that even after complete thyroidectomy or after a long radiogold gives a somewhat better therapeutic ef course of propylthiouracil or thyroid-stimulating feet because the greater penetration of the gamma hormone (43). The cases in which there is a good radiation will, with the beta radiation, in effect uptake of radioiodine, however, give one increas give a more uniform dose. Radioactive Y@ (@3) ing confidence that if selectively localizing corn and chromic phosphate (45) beads and radon im pounds can be found, lasting benefits might be plants (10) have been used for destruction of the obtained in advanced cancer of other types pituitary in certain types of cancer. The tech also. nics for distributing radioactive materials in tis Figure 1 is a gamma ray picture of the localiza sue may be improved in the future in some cases tion of I's' in the body of a patient with thyroid by the intra-arterial injection of the radioactive rnetastases obtained in the first whole-body scan materials. ner now so widely used. This whole-body scintilla In 1948 we used colloidal chromic radiophos tion scanner, developed by Anger and Tobias (8) phate in the treatment of a group of patients with for photographing gamma ray-emitting isotopes in chronic leukemia, polycythemia vera, and also a the body, is shown in Chart 4. It consists of a series group with marked splenomegaly or hepatomegaly of scintillation counters within lead cylinders. The from miscellaneous causes (6, @).We found these gamma ray energy from the isotope within the results no better than those following P@, as body is converted to light energy and photo Na@RP@O4, and, because of the chances of getting graphed with a polaroid camera as the body is the radiocolloid outside the vein with resultant scanned. New methods for visualizing the distri radionecrosis, we have more or less abandoned the bution of radioisotopes in vivo, such as the one de use of the various radiocolloids for the treatment scribed here or the gamma ray pinhole camera of this group of diseases. Gofman and associates (85), are expected to be of indirect use to therapy used many other radiocolloids in the same group through more accurate localization of tumors. The of diseases and arrived at the same conclusion (6). patient illustrated in Figure 1 was a 68-year-old Cobalt-60 is being used in intracavitary and in male with thyroid metastases in the left upper terstitial therapy of nasopharyngeal and maxillary arm, the chin, the sternum, the hip, the thigh, and tumors and uterine, prostatic, bladder, and bron the ribs. Interestingly enough, two of these lesions chogenic carcinomas. In general, it is too early to were not discernible by x-ray examination, yet evaluate the results in comparison with those they could be picked up by the scanner. This achieved by conventional means of therapy. Hin method of locating tumors would of course have man and co-workers (18, 47) treated 85 patients important diagnostic applications if localizing with bladder tumors by intracavitary irradiation compounds emitting gamma rays could be found using cobalt-60. They report that in four of nine for other types of cancer. This particular patient patients with tumor confined to the mucosa the had the largest uptake of radioactive iodine in lesions were destroyed, but most infiltrating le metastatic lesions that has come to our attention. sions were only temporarily arrested. Comparative counting rates over the tumor and The cobalt bomb teletherapeutic units are of an equal volume of normal tissue showed that the wide interest now and are being used as substitutes tumor concentration of I's' was as much as @00 for @00kv. x-ray equipment in the treatment of times that in an equal volume of normal tissue. deep-seated tumors. Radiocobalt provides the During therapy with an oral dose of 100 mc. of gamma ray source in these units, but other gamma J131, as much as 100,000 rep in radiation was deliv ray emitters such as cesium are also being used, ered to the neoplastic lesions. Prior to surgical especially in Great Britain. These teletherapeutic thyroidectomy there was no uptake in these me units have certain advantages over x-ray equip tastases. Now, 6 years later, this man is symptom ment, such as cost and mobility, but one cannot free, and, at the age of 74, he is an example of the expect much improvement in end results over con good result that can be obtained with isotope ther ventional methods which use x-ray or other gam apy when there is a high selective uptake by neo ma ray sources. plastic tissue. Uptake in metastases can be stimu Since the first therapeutic use of radioactive lated by surgical thyroidectomy, and administra iodine (15, 16, 17, 80), it has been widely applied tion of propy!thiouracil and thyroid-stimulating in the treatment of hyperplastic thyroid disease hormone are also sometimes helpful in increasing or Grave's disease; indeed in many hospitals iodine uptake in metastases (48). Another diffi it is entirely replacing surgery, and remarkably culty encountered in the treatment of metastatic

Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 1956 American Association for Cancer Research. LAWRENCE AND T0BIASâ€”Radioactive Isotopes in the Treatment of Cancer 189 thyroid cancer with radioiodine is that the radia planted melanosarcoma. There was some localiza tion dose may not be uniformly distributed in the tion in the melanosarcomatous tissue, but there tumor tissue. Surgery and x-ray continue to be the primary tools for treating thyroid cancer. TYROS/NE The high selective localization of iodine in thy roid tissue and also the selective uptake of radio phosphorus by the bone marrow and blood-form HOQI'â€”C--Câ€”Câ€”OH 4@O ing tissues allow us to deliver relatively high doses ii of radiation to specific tissues. Perhaps in our H NH2 present state of relative ignorance regarding the metabolic differences between the cancer cell and was an appreciable uptake by the adrenal and normal cell, it is too much to expect that a radio thyroid glands, since tyrosine is a precursor of the active compound can be found which will localize hormones produced by these tissues. in cancer cells selectively enough to give V5, 50, or The metabolism of stilbamidine containing C14 more times the radiation than normal cells will was studied in multiple myeloma, and, while it did

SCHEMATIC DIAGRAM

CHART4.â€”Diagram of the scintillation scanner (from Anger et at.)

receive. If such is to be found, the ideal isotopes to localize in the myelomatous tissue, there was an be built into the localizing compound would seem even greater uptake by the liver. to be hydrogen-S or carbon-14. The latter provide These examples are typical of the many coin relatively soft beta rays traveling only a few cell diameters in tissue. ST//JAM/DINE Many workers have attempted to synthesize compounds containing radioactive carbon and other radioelements for selective localization. Reid and Jones (44) made C'@-labeled tyrosine and in jected some of it into animals carrying a trans

pounds that have been synthesizedâ€”localization astatic breast cancer by adrenalectomy (@0). of the radioactive compound is not sufficiently lim Olivecrona and associates were the first to report a ited to the neoplastic cells to permit a good dose of remission in metastatic breast cancer following radiation to be given without damage to normal hypophysectomy and have recently reported the tissue. results of this form of therapy in a series of 30 pa Some of the most interesting current investiga tients (8@2).Other workers in this field have esti tions on selective localization are typified by the mated that approximately 50 per cent of patients studies of Pressman and associates (41) . After im with advanced breast cancer have tumors which munizing animals to various normal tissues and are hormone-dependent, and approximately 50 per neoplastic tissues and then adsorbing radioactive cent of the patients of this type undergoing sue iodine to the antibodies, they have been able to cessful hypophysectomy will show some evidence demonstrate some localization of these antibodies of healing (38, 89). Apparently, the response is in dependent of the cellular type of mammary tumor, â€¢Chroniclymphatic leukemia (131) and whether the effect is always mediated through Chronicmyelogenousleukemia (138) the ovaries and adrenals or whether there is a pri â€¢Breastcancer, radical mastectomy (125, Univ.of Rochester) mary pituitary factor is not yet known. z0 â€¢Stomachcancer (2772, Mayo Clinic > Lung cancer, pneurnonectomy With the hope that hypophysectomy could be > (202, G.A Mason) achieved by irradiation, for 15 months we have U) been making such attempts using a somewhat I z w unique form of irradiation from the 184-inch cy C.) 3 This work is a projection of the animal LU a. studies of Tobias et at. (51, 54), who achieved hy pophysectomy in the rat, dog, and monkey with beams of high energy deuterons or protons. One unusual feature of the beam is its pencil-like nature YEARS with very little scatter, unlike a similar beam of CHART 5.â€”Survival rates in chronic lymphatic leukemia x-rays or gamma rays. Another unusual feature of treated with P@ (@8), in breast cancer treated by radical these beams is that there is a relatively greater mastectomy (49), in stomach cancer treated by gastric resec depth dose compared with surface dose. The com tion (57), and lung cancer treated by pneumonectomy (33). parative doses at the surface and depth for @00kv. in the various normal and neoplastic tissues. More x-rays, 16 mev electrons, and 190 mev deuterons recently Bale2 has achieved tumor localization of are given in Chart 6. The @00kv. x-rays fall off such antibodies 15 times greater than that of any markedly at 10-cm. depth, and the electrons from normal tissue, indicating that this approach may the betatron or synchrotron also fall ofT consider be a very hopeful one (4, 50). ably, but the deuteron irradiation rises to a peak The therapy of cancer continues to be based at 14 cm., so that the depth dose is approximately primarily on early diagnosis, surgery, and post 4 times that entering at the surface. operative x-ray therapy. Radioactive isotopes and Two animals with mammary cancer are shown nuclear energy have not yet added importantly to in Figure @.The one on the left is the control, and the armamentarium of cancer therapy, but the the one on the right has been irradiated by passing relatively poor survival in cases of deep-seated the beam through the chest of the animal from the cancer impels investigators to make heroic at opposite side, localizing it on the tumor. In other tempts to relieve these people and extend their words, it is possible to deliver energy in the depths lives. As can be seen in Chart 5, the 50 per cent of tissues with relatively little skin effect using this survival in the case of breast cancer, the most com form of radiation. Tobias et at. have applied this mon type of cancer in women between the ages of beam to the pituitaries of rats, monkeys, and dogs 40 and 60, lung cancer, and stomach cancer is and have been able to remove the pituitary by this approximately 8-5 years. selective form of external irradiation, producing One of the real advances in cancer therapy has atrophy of all the target organs, effects paralleling been the revelation of the relation of hormones to those of surgical hypophysectomy. Four litter certain types of cancer, including the effects of mates are shown in Figure 8. The second from the oophorectomy, adrenalectomy, and hypophysec left has had surgical hypophysectomy, and the tomy on advanced breast cancer (4@). Two ex third from the left irradiation hypophysectomy. amples in particular are the work of Huggins in the The animal on the left has been subjected to hypo field of prostate cancer treated by orchiectomy and thalamic irradiation which produced obesity, and diethyLstilbesterol (19), and the treatment of met the animal on the right is the control.

* W. F. Bale, personal communication, presented at @Thiswork is supported by the Atomic Energy Commission, â€œAtomsfor Peace Conferences,â€• Geneva, August, 1955. the California State Cancer Fund, and the Donner Foundation.

During the past year this beam has been applied the danger of cranial nerve damage. However, al to the pituitaries of patients with advanced breast ready in the first fourteen patients treated there is cancer and to two patients with leukemia, one hay evidence of marked pituitary suppression (Chart ing an associated diabetes. This work has been the 7). Figure 5 shows the patient in position for treat subject of two previous reports which give much ment. Prior to irradiation the sella is very carefully more detail (5@2,53). The patients with cancer brought into position by taking x-ray photographs, have previously had every form of convention al therapy, including radical mastectomy, post operative x-ray, hormone therapy, as well as oÃ¶phorectomy and adrenalectomy, and they were no longer responding to these forms of therapy. The aim in this work has been to find out how sue cessfully one can inhibit or destroy the pituitary by this selective form of radiation as compared with surgical hypophysectomy. Figure 4 shows a lateral view of the sella turcica in one of the pa tients with the beam centered on the crosshair. It is possible to cover most of the area occupied by the pituitary within the sella with very little radia tion being delivered to the surrounding tissues, such as the hypothalamus and optic chiasm. Up to the present time, use has not been made of the Bragg curve, and the relatively great pituitary DEPTH IN CENTIMETERS

dose is accomplished by continuous head rotation, CHART 6.â€”Comparative doses at surface to 15 cm. depth the beam being centered on the pituitary. There for @OOkv.x-rays, 16 mev electrons, and 190 mev deuterons are real problems encountered in avoiding irradia (which are like protons in depth effects). tion of the vital structures surrounding the hy pophysis, such as the optic tracts, the hypothala and with the aid of crosshairs the beam is made to mus, and the various cranial nerves. It has not fall on the exact center of the sella. During treat been possible to give as much radiation to this area ment the head is held tightly in a plastic mask and as one would like at the present time because of continuously rotated through a 60Â°â€”70Â°angle,30Â°â€”

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CHART 7.â€”Patient M.W. Changes in pituitary gonadotrophins, Pâ€• uptake, and protein-bound iodine during and after treatment with 13,850 rads.

85Â°tothe right and S0Â°â€”35Â°tothe left. The first pa applying the products of nuclear physics, especially isotopes, tient treated (Chart 7) was given 18,850 rads, one to therapy, particularly in the use of 1131in Grave's disease, Pâ€• r&d being roughly equivalent to a rep, delivered to in the treatment of polycythemia vera and leukemia, and the cobalt teletherapeutic units for external irradiation treatment the pituitary over a period of about a month in of cancer. fractionated doses. As far as we know, the findings REFERENCES in this case are the first clear-cut evidence that 1. AEBERSOLD,P.C. U.S. Atomic Energy Commission.Eight target organ effects can be brought about by pitui Year Summary of U.S. Isotope Distribution. Goveimment tary irradiation (note decrease of pituitary gon Printing Office, 1955. adotrophins and marked decrease in thyroid func @.ANDREWS, G. A.; RoOT, S. W.; Knaai@i, H. D.; and tion as shown by fall in I's' thyroid uptake, Chart B1GEWw, R. R. Intracavitary Colloidal Radiogold in the Treatment of Effusion Caused by Malignant Neoplasm. 7). Ann. Surg., 137:375â€”81, 1953. Whether or not there will be a real application 3. ANGER, H. 0. A Multiple Scintillation Counter in Vivo@ of irradiation hypophysectomy, or even surgical Scanner. Am. J. Roentgenol. Rad. Therapy & Nuclear hypophysectomy, in cancer therapy is not yet Med., 70:605â€”ig,1953. @ known. Another or 8 years must elapse before 4. W. F., and Sp@tn,I. L. In Vivo Localization of Rat Organ Antibodies in Ovaries, Adrenals, and Other Tissues. preliminary impressions regarding clinical benefits J. Immunol., 73:125â€”33,1954. in this series can be gained. Also, it will require an 5. CHAPMAN, E. M.; M@oop, F.; M@is@ra@un@A,J.;and other 5 years before it is known whether hypophy MARTiN, J. M. Ten Years' Experience with Radioactive sectomy will appreciably lengthen life in advanced Iodide. J. Clan. Endocrinol. & Metabol., 14:45â€”55, 1954. 6. DOBSON, E.; Knu@y, L. ; JONES, H. ; and Gorst@, J. cancer of this or other types. Radioactive Substances Specifically Localized in Liver, While I do not intend to belittle the achieve Spleen, or Bone Marrow, pp. @6â€”@7.XVII Interuat. ments of workers with artificial radioactivity and Physiol. Congress, Oxford, England, July, 1947. nuclear energy in cancer therapy, the results re 7. F@a, L. E.; Swsmr, W. H.; ROBERTSON, J. S.; FOSTER, fiected in extension of life so far are not impressive. C. G.; LOCESLEY,H. B.; Sum@i@n, D. L.; MENDELSON, M. L.; and STICKLEY,E. E. Neutron Capture Therapy However, when one must deal with the problem of with Boron in the Treatment of Glioblastoma Multiforme. intractable pain, he learns to appreciate any pal Am. J. Roentgenol. Rad. Therapy & Nuclear Med., liative procedure which will make the patient more 71:g79â€”91, 1954. comfortable even if significant extension of life is 8. Fwcxs,R.H.;KmtR,H.D.;EixiNS,H.B.;andCuu',D. Treatment of Carcinoma of the Prostate by Interstitial not demonstrated. Radioisotopes and the new ac Radiation with Radioactive Gold (Au198). J. Urol., 68: celerators and external sources of radiation have 51oâ€¢-@. given us tremendously important new tools and, 9. . Treatment of Carcinoma of the Prostate by Inter from the humane standpoint, have been a real stitialRadiation with Radioactive Gold (Au198): Follow-up boon to cancer therapy. If a selectively localizing Report. Ibid., 71:6@8â€”SS,1954. 10. FoRREST, A. P. M., and BROWN, D. A. Pituitary Radon compound or compounds can be found which Implant for Breast Cancer. Lancet, 268: 1054â€”55,1955. would emit a soft form of radiation, the really im 11. FRIEDELL,H. L., and STORAASLI,J. P. The Use of Radio portant advances that could be realized are ob active Phosphorus in the Treatment of Carcinoma of the vious. Much more basic research including that Breast with Wide-spread Metastases to Bone. Am. J. with tracers is needed to learn more of the physiol Roentgenol. & Rad Therapy, 46:559â€”75, 1950. 1@. FRIEDELL, H. L.; THoseas, C. I.; and KnoHirnt, J. S. De ogy of cancer. In the search for therapeutic bene scription of an Sr9Â°Beta-Ray Applicator and Its Use on fits, our relative ignorance of the nature of neo the Eye. Am. J. Roentgenol. & Rad. Therapy, 65:@3@â€”44, plastic growth is emphasized, and the solution to 1951. the problem will probably not be found without 13. GODWIN, J. T.; F@uu1, L. E.; SWEET, W. H.; and ROBERT greater understanding of the cancer process at the SON, J. S. Pathological Study of Eight Patients with Glioblastoma Multiforme Treated by Neutron-Capture cellular level. Therapy Using Boron-lO. Cancer, 8:601â€”15, 1955. 14. Goura, H., and ILtsIN, P. F. Distribution and Effect of ADDENDUM Colloidal Radioactive Gold in Peritoneal Fluid Containing At the International Conference on Peaceful Uses of Atomic Free Sarcoma 87 Cells. Proc. Soc. Exper. Biol. & Med., Energy held at Geneva in August, 1955, the author talked at 74:634â€”38, 1950. length to numerous Russian investigators and learned that 15. HAMILTON,J. G., and LAWRENCE,J. H. Recent Clinical during the past 3â€”Syears they have been very active in Developments in the Therapeutic Application of Radio

Fio 1.â€”A scintogram of a patient with thyroid metastases at various times after injection of a tracer dose of 1131. The scintillation scanner passes back and forth over the body, translating the gamma ray energy from the I's' within the body into light energy, which is then photographed with a Polaroid camera.

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Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 1956 American Association for Cancer Research. Fia. g.â€”A: Control animal with untreated mammary tu mor; B: Healing tumor after bombardment with 190 mev deuterons. The beam of deuterons was directed to the tumor through the opposite side of the animal's body. FIG. 8.â€”Four littermates (left to right): hypothalamic ir radiation, producing obesity; surgical hypophysectomy; ir radiation hypophysectomy; control. FIG. 4.â€”Diagnostic x-ray of a patient's head in position for treatment. The crosshairs mark the center of the beam. The outlines of the sella turcica are clearly shown. The black spot on the film on the left shows the shape of the beam, which can be adjusted to fit each patient. The radioautograph is made by briefly turning on the proton beam prior to developing the film. The beam spot is actual size, while the x-ray picture of the sella is enlarged by @0per cent owing to the finite focal distance of the x-ray machine. FIG. 5.â€”Patient in position for irradiation with the proton beam.

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John H. Lawrence and Cornelius A. Tobias

Cancer Res 1956;16:185-193.

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