University of California School of Medicine, San Francisco, Radiological Laboratory Progress Report for July 31, 1959, Atomic Energy Commission Contract No. at-11-1-Gen-10, Project No. 2

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University of California School of Medicine, San Francisco Department of Radiology for period ending July 31, 1959 A REVIEW OF TEE LABORATORY'S ACTIVITIES AND PROGRAM Atomic Energy Canmission Contract No. AT-U-1-GEN-10, Project No. 2

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TABLE OF CONTENTS CLINICAL RADIOLOGY SECTION Acute Radiation Injury Syndrome - Recovery and the Sparing Effect of Fractionated Late Effects - Animal Experbents Late Effects - Follow-Up Studies i n Man Comparative Mammalian Studies Survival Curves i n Cancer of the Breaet

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TEE RADIOLOOICAL IABORATORY University of California School of Medicine _ -The Radiological laboratory was established i n 1949 t o investigate methods for improving the radiation treatment of cancer, with special reference t o the usefulness of a 70-Mev synchrotron as a source of x-rays and during which patients have been treated with 70-Mv x-rays. The Cllnical Radiology Section has taken charge of the selection, study, treatment, observation, and follow-up of the patients. pied by various aspects of dosimetry i n addition t o the operation, maintenance, and development of the synchrotron. The Biology Section program centers on the response of various biological systems t o radiation with particular emphasis relating t o the problems of radiological practice, particularly (1)the RBE of clinically employed qualities of x- and p r a y s , (2) certain methods of controlling the biological effects of radiation, and (3) the l a t e effects of radiation, both i n anhale and man. A synchrotron development period has been followed by three years The Physics Section has been occuThe Iaboratory is the lineal descendant of a project t o study the effect of whole-body x-irradiation of humans, started i n 1942. The patients treated then are seen only very occasionally. later, the effect of p2 and, l a t e r still, of IL3‘as total-body irradiators wm studied by hemstological methods. To that early activity, research in thyroid physiology using functions o r other research programs, with the exception that a follow-up study of radioiodine-treated cases is s t i l l aided by Iaboratory personnel. The iodine studies have slowly been absorbed into service I n 1949 the U. S. Atomic Energy Comission entered the f i e l d of cancer research, particularly with reference t o the effects of radiations. One field not being cultivated elsewhere i n the world was that concerned with x-rays and electrons with energies above 31 MeV. This Laboratory was establlshed t o study clinical effects of 70-Mev radiatioee and the related physic a l and biological problems. and adjacent t o the hospital so as t o take advantage of t h e academic surroundings, with all that this mesne t o scientists. It was established within the medical school

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CLINICAL RADIOUXFY SECTION Robert S. Stone, MA., Section Chief Patients having cancer w e r e first treated with 7O-W x-rays from the synchrotron on the eleventh of July, 1956. Up t o the end of July, 1959, lo9 patients had been treated, most of whom had advanced disease, and the mortaUty, as expected, has been very Ugh - 66 are already dead. The 43 living patients are being followed a t frequent intervals. Table 1 shows the survival data for all the patients up t o July 31, time too short t o permit an assessment of the curative value of these m u l t i - million-volt x-rays i n cancer therapy. Before attempting such an evaluation, a large number of patients m u s t be treated and followed for a t least five years and, preferably, longer. Much has been learned, however, about how the patient and h i s tissues react t o this quality of radiation, and some individual patients have shown remarkably gratifylng early results. It is of intere s t that 7 of the 27 patients treated before July 31, 1957 sunrived two After patients have conpleted their treatments, they are followed a t weekly or biweekly intervals =til the immediate reactions subside. For the next six months they are seen every two months. After the first year, the intervals between observations are varied according t o the patient's condition but, i n general, are 6-month periods. patient through his entire remaining life. To date, the number of patients treated is too small and the elapsed Our aim isto follow every Lack of available patients has been a W t i n g factor in the trehtment program, not availability of the synchrotron; the operational characterist i c s of this machine under the skillful management of the operating crew have been such that it has been available daily f o r scheduled treatments, with only one single day excepted. Patients have been drawn fran two so-wces: staff patients of the University of California Hospitals, either in- o r out-patients, and private patients referred by their doctors t o radiation therapists at the Medical untried energy of 70-mlllion volts, patients have been utilized whose cancers w e r e of such a type or a t such a stage of growth that the chance of surviving 'five years would have been less than 5 6 v i t h any standard therapy. In addition, patients were selected t o take advantage of the unique physical characteristics of the radiation from the synchrotron - f o r example, pati ents whose lesions had t o be treated through several centimeters of nom1 tissue; obese patients i n whcxn the radiation must penetrate t o relatively great depths before the region i s reached i n which maximum absorption is In the selection OS patients f o r treatment with this previously

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desired; patients with lesions in places where either bone or a i r is interposed between the surface and the tumor (e.&., lUlg, PharynX). As was t o be expected, those with cancers of the head and neck and of the uterus have shown the best survival; those with cancers of the lung, bladder, and brain have responded much more poorly. tumor is of interest in connection with the results. When we started treatments we had no way of measuring the dose in rads; it wa8 measured in esu per cc (electrostatic units per cubic centimeter) and compared with tissue r a n t - gens of 1OOO-kv x-rays. After the flrst group of 6 patients, the relation between the esu per cc and the rad w a s supplied by the Physics Section. the Radiation Therapy Division of the Ilospital, it vas cutomary t o give a dose of about 5000 roentgens t o a t w r in 5 weeks, using supervoltage (1000 k v p ) . When soft tissue is being considered, 5000 tissue roentgens is equivweeks. Subsequently we increased this t o 5250 rads - alO $ increase - still given in 5 weeks, because the reactions t o the 4800 rads were not as great as we expected and desired. all patients who could tolerate such a dose. total tiM have t o be varied according t o the patient's condition and reaction. Table 2 shows the number of patients that have received certain levels of dosage in given times. t o 5000 rads, 33 of these in 5 weeks, 13 in 6to7weeks. received 6000 rads, 39 in 6 weeks and 16 in 7 t o 8 weeks. treatment was stopped because of the patient's condition before even 4500 rad6 had been administered. The absorbed dose administered t o the volume of tissue containing the Therefore our f i r s t patients were given 4800 rads in 5 later, we decided t o give 6000 reds in 6 weeks t o Of course, the daily rate and Forty-six patients received total tumor doses of 4800 It is obvious from Table 1that these doses did not cure aU of the patients. Moreover, a study of the records shows that in some patients the cancer did not disappear even in the most heavily treated regions. nite advantages in using them that will be discussed below. Here, let us say that some therapists report using higher t o t a l doses and sometimes in shorter elapsed times. We f e e l that we cannot, in justice t o the patients, go t o higher dosee u n t i l we have observed those patients already treated for longer periods of t i m e . Moreover, from same reports, it would seem doubtAiL that larger doses would accompllsh'any more cures - and might cause much more damage t o normal tissues. A difficulty in accept- the statements of the number of "units" of radiation given by various radiologists is that we cannot be sure that we are a l l using the aeae physical unit, even when similar types of instruments are used. interlaboratory comparison8 being made by Drs. Adems, Sinclair, e t al. are clearing up some of these problems. When extended t o more laborstories, we w i l l be better able t o interpret the doses given in various Laboratories. Such ccunparisons should be extended t o all multimillion-volt units and a means found t o calibrate better the supervoltage and.cobalt

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A. Patient and Tissue Reactions We cannot report statistical studies of the degree of "radiation sicksame reactions regardless of the "energy)( of the rays. patients have been unable t o complete treatments, but most patients proceed with little fatigue and practically no nausea. It is our impression that equal gram rad doses produce about the phagia, diarrhea, dysuria, and sore throats. _ - The observed tissue reactions such a s erythema, epi the lit is, and mucositis have been directly related t o the absorbed dose, as predicted from fies the physical depth-dose measurements. tion with this quality of radiation has been observed. we cannot expect the quality probably be just as resistant t o 7O-Mv x-rays. - .I n other words, the relative degree of tissue reaction veriNo reaction peculiar t o irradiaThis indicates that se t o produce any more differential effects. The question of how much effect t h i s radiation will have on bone when passing through it t o reach a cancer on the opposite side has not been anewered by clinical experience. this radiation t o the same extent as it would supervoltage radiation, and the differential between soft tissue and bone absorption should be about the same for these two qualities of radiation. By calculation, the bone should absorb The distribution of absorption of the energy i n tissue as shown by isodose curves is considerably different from that f o r either Co60 y-rays charts f o r these radiations. It i s readily seen that the meximum dose is deepest f o r the 70-M~x-rays, but it should also be noted that for these uame x-rays the range of depth t o which a high percentage of the maximum dose is delivered is much longer. 8 cm, from the 6- t o 14-cm depth, whereas f o r 22-Mv x-rays it extends 3 cm, only from 3- t o 6-cm depth. The former range frequently covers the resion *ere deep tumors are located and hence no cross-fire is necessary i n many cases, whereas the latter range i s relatively close t o the surface and of limiteil extent. The 95%l e v e l for Coeo y-rays is just under the surface, Figures 1 and 2" show split field comparisons of isodose The dose a t the portal o? e x i t of the beam is considerably greater However, it i sfor 7O-Mv x-rays than f o r either of the other qualities. still not M large as the tumor dose -even for single field use - and when cross-fire is used the skin dose is less than one-half the tumor dose. As a matter of fact, the skin effect has ceased t o be a problem except i n the Isotope distribution f o r Cod' taken from S. 0. Fedoruk, Isotope distribution f o r 22 Mv taken from J. S. Iaughlin,

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head and neck regions where the skin i s so close t o the tumor that it is imporsible t o avoid a high dose t o it with any kind of radiation. One can make the general statement that the t o t a l insult t o the patient is least when the maximum dose for each f i e l d sinsly occurs within the region t o be In planning treatments for individual patients, the radiologist takes a "contour" of the patient a t the body level t o be treated and Specifies the Next, the physicist, with the aid of isodose charts, predicts the best way of getting the maxirum dose t o the specified region with the least insult to the whole patient and t o the specified structures. The final plan of treatment is arrived a t by consultation t o see that the calculated plan i s poss i b l e in each instance. Table 3 shows the number of patients who received treatment through 1, 2, 3, or 4 fields. It is noteworthy that 56 patients, or 51$, were treated through one single f i e l d and that 49, or 45$, were treated by a two-field technique. From the above facts, it can be seen that the advantages of using 70-M~x-rays in the treatment of cancer result from the pattern of absorption of energy from these rays. advantage can be utilized: boundaries of the region t o be treated and the structures t o be avoided. - - The following are situations in which this (1) It is easier t o deliver any desired dose t o a deep-seated lesion. (2) Stout patients can be treated as adequately as thin ones. ( 3 ) When it is necessary t o avoid certain surface areas, such as previously irradiated skin, it is easy t o t r e a t through wide or thick parts of the body where the skin had not been previously irradiated. Simple one- or two-field techniques can be used on 954 of the he use of single fie- makes it easier t o avoid vital tissues in many instances. c. Locations of Greatest Usefulness Because of the above advantages, it is obvious that the greatest usefulness will be found i n the thicker parts of the body. however, that, a8 shown i n Figs. 1 and 2, the maximum dose may not be reached u n t i l 6 cm have been penetrated and that the next 8 cm are quite evenly and equally irradiated; this allows one to treat "through" the good side of gn involved neck, sparing much of it, and thoroughly irradiating the involved side by the use of a one-field technique. Similar single-field techniques can be used for the region of t h e paranasal sinuses and face by using …