University of California School of Medicine, San Francisco, Radiological Laboratory Progress Report for July 31, 1960, Atomic Energy Commission Contract No. at-11-1-Gen-10, Project No. 2

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Biology and Medicine Department of Radiology , for period ending July 31, 1960 Atanic Energy Commission Contract No. AT-U-1-GEN-10, Project No. 2

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TABLE OF coN!lmTs pase 111. Locatlone of Greatest UseALLncrs IV. Disadvantages i n the Use of the Synchrotron III. Neutron Meaeurements IV. Other Activities BIOLOGY SEC EON zi I. Prompt and Acute Effects of X-Rays 1. Bone Marrow Studies A. Absolute Cell Counts from Bone Marrow F i l m B. Response of Mouse Femoral Bone Marrow t o WholeBody X-Ray Exposure: Cornparlean of Two Straine 11. Late Effects of X-Rays 1. Latent Period of X-Ray Induced Life Shortening i n the Mouse, Rat, and Chinese Hamster, Aesoclated with Aging and X - Ray Exposure B. Renal Changes i n the IAF, Mouse after Dally 3. Age and Epithelial Cell Renewal in the Mouse Intestinc 4. Age at Exposure and the f a t e Effects of X-Rays: CAF, Mice Irradiated at 1t o 2 Years of Age 111. Life Shortening in Man after Radiation Therapy IV. Genetic Effects of X-Rays Life Span of Progeny of X-Irradiated Male Mice

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THE RADIOLOGICAL LABORATORY University of California School of Medicine, The Radiological Laboratory a t the University of California Medical Center, San Francisco, i s one of the research and development installations of the U. S. Atomic Energy Canmission. The Conmission provlded the funds t o erect and equip the building and continues t o provide the operating expenses. For operational purposes, the Laboratory i s divided into The Clinical Radiology Section i s concerned with the treatment of pati ents with cancer by 70-Mv x-rays fran the medical synchrotron, vith the object of determining the curative value of these multimillion-volt x-rays. The Physics Section is concerned with the practical problem of synchrotron operation and maintenance and wlth research concerning radiation doelmetry. The Biology Section centers i t s program on t h e study of the response of various biological systems t o radiation, placing emphasis on problems relating t o those of radiological practice. CLINICAL RADIOLOGY SECTION Between July, 1956 and the end of July, 1960, 154 patients have been treated with 70-Mv x-rays f r a n the synchrotron, most of whcnn had carcinomas that were known t o be hard t o cure. ready dead, leavlng 63 alive. through his remailling life, and thus far we have been successful in doing thia. Table 1 shows the mortality and survival data for the t i e n t s who have survived more than 2 years (9$), whereas last year there were only 7 of 109 (6%). 3years, one of them more than 4 years. Of these, 91 are alIt i s our aim t o follow every patient . It is noteworthy t h a t this year we have 14 paSix patients have survived more than In Table 2 the approximate doses delivered t o the various tumors 'are listed. It can readily be seen that the majority - 82 of the 154 - Because the dose t o the brain i s seldan allowed

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t o exceed 5OOO rads and because 15 patients with brain tumors were treated during the paat year, there is an increased number of pati ents who received tumor doses of 5000 rads or slightly less. A more complete discussion of dosage may be f- i n UCSF-W (199). One of the advantages of the TO-M9 x-raya that cams f i a n the dose distribution In the tissues is that only one or two fieIda an needed in order t o @ye the de sind dose t o the tumor. Table 3 sbcnre that 60$ of the patients were treated with a 1-field technic, 36% with a %field technic, aad only k$ with more than 2 fields. Because of this, the accuracy of the beam direction is easier t o attain, and the time taken in setting up patients is nut very long. HsvFng used the TO-Mev synchrotron for four year%, we bellem now that there are definite advantages i n using x-raye of this energy in many cases. A l l of these avantages are of a technical nature and come fram the distribution of dose within the b d y (see ESF-19). The follavLng arc situations In w h i c h these advantages caa be (1) It is easier t o deliver any desired dose t o a deep-seated (2) Stout patients can be treated aa de qp te u ~ n deasily as ( 3 ) When it is necessary t o avoid certain surface areas, such as previously Irradiated skin, it is easy t o treat through vlde or thick parts of the body where the skin had not been previously irradiated. patients. Simple 1- or 2-field technics can be used on 95% of the of aiming at and encompsesing the tumor than Is possible with many use oi single fie- makes it easier t o avoid vital tisIms use of simple technics makes possible greater accuracy 0 III. bcationa of (hratest Usefulness Because of the abave advantages, it is obvlous that the greatest m ue fd ness will be found in the th lc kr parte of the bcdy. It should ) be noted, however, that the useful dose region is not reached u n t i l

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Table 3. Technic Accarding t o Number of Fields Region of Cancer Nlmbtr of Patients *See Footnote t o Table 1 (t) itemizing cases included under

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6 an. have been penetrated and that the next 8 a.BI.C quite eve- and equ3J.y irradiatedl this allma one to treat “thrcqh” the good side ai an imrolnd neck, sparing much ai it, and thoroughly irradiating the Involved side by the use of a 1-field techale. Similar single-field technics can be used far the region of the m a l slnrrser and face tients this results in the Irradiation of mare brain tieeiue than would result franndge filter technics with multiple fields on 250-hr maby Uaa moula%et, an tbe SUri aCr to fiuild Up t k dose, but in 8- pS- ~ h cuniformity or tk irradiation ai a given volrtmr ai tissue a e p in the bcdy vhould in the treatment of extensive diaeasc in the pelvis and chert. with the following types of cancer a m therefore colleidered t o be the mes who can profit most by the use of this ey nc km bm. this W t y of radiation of special advantage (3) Invasive cancer of the bladder (4) Cancer of the lung or bronchue, when Inoperable (51 Advanced cancer of the paranasal sinuses ( 6 ) Malignant tumora of the brsin Disadvaatages in the Use of the synchrotron he synchrotron is electric- more compucated t o operate and t o senrice than cowentianal equipment. must be mare highly trained than the nrrrse-technician employed in canvcntional radiatian therapy. (1) Thun, the operating crew desirable - this condition w i l l soon be rectified. A t present the timt required t o change fields I s greater tbu (2) Accept cases in emuer stages of disease a ( 3 ) courage referral oi o b r e patients for treatnmznt (4) Evaluate the effects ai dosage employed on the Increased number of patients surviving more than 2 years, wlth a view t o cbmging the dossge pattern

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The clinical work was cerried on under the sllpemdsion of Dr. Robert S. Stone. Dr. Rose V. Louie was directly in charge of the patients and Bdministercd most of the treatments. &e. Jane Gardon served as nursetechnician. The hematologist-technician w a s Miss Jean Fullertan. The

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_ -The prlme responsibility of this section has been and continues t o be the development, calibration, maintenance, and operation of the 70-Mev s p - vlth the administration of treatments t o the first group of patients. unit has functioned reliably since then. I n addition t o this selrice work, personnel of this section carry out some research in the f i e l d of radiation dosimetry and some engineering developnents for the synchrotron. The initial developrent and calibration p e r i d ended in July 1956 -.The "he material t o follow summarizes the activities of personnel O f this section during the past year. !An intermittent leak in the pumping system vas traced t o one of the There were M other diificulties with the pumping system itself. rotating vacuum couplings. crack did develop in the acceleration chamber (donut), but this was cleaned and sealed with epoxy resin. There have been numerous changes of injector, but these require a "down tlme" of only 60 t o 75 minutes. It has been possible t o arrange down times for other changes in the vacuum system so as not t o interfere with the patient-treatment schedule. This was repalred by machining a new replacement These units are the actual source of electrons which the rest of the ne assemble and test our own. of components, and an unfortunately large amount of t h e has had t o be devoted t o this effort, primarily because available canpcments are marginal. In the absence of any commercial manufacturer, There remains a problem of a suitable supply -sating filter with the x-ray beam axis continues t o function with minimal t o change field shapes. A prototype method for a quick-change method has been shown t o work. of achievlng compensation of the naturally peaked x-ray beam. There ranelns, however, the objectionable amaunt of time required The method requires a substantial revision in the way

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trials for each replacement f i e l d require multiple studies of radiation distribution in a water phantom. This is a formidable task. cided that time wouLi be saved in the long run if a suitable isodose plotter were constructed. A unit based on the automatic sequencing idea of A. Cole (Phyeics Department, M. I). Andereon Hospital, Houston, Texas) haa now k e n the testing of an appropriate probe ionization chamber and the resolution of two minor electrical problems. Its use on the synchrotron for the above purpose awaits only The ferrous sulfate-benzoic acid dosimeter developed here four years ago continues t o be used as a working standssd for exposure control on the synchrotron. Expos ~ r e ~are made daily before the treatments for patients are begun. We are, in fact, sampllng the beam by qusdrante t o check the adequacy of the servmnechanism compensation control as w e l l as the exposure An important step towards integral absorbed dose measurements when the technology of using 83 ion exchange resin column t o concentrate ferric ion in the presence of ferraus ion was worked out. The method l e successful under laboratory conditions in whlch pyrex I s used everywhere. A suitable non-glass container is now under investigation for use wlth x-rays under practical circumstances. Assumlng that there is no container problem, the measurements should be capable of 1% precision f o r only a few rads average absorbed dose. It has been proposed that an intercaparison of exposure units be made during the coming year between the National Bureau of Standard8 and this struction and initial testing of a euitable Ionization chamber, the callbration of components f o r the preclrlon integration of char& trarrsferred by thie chamber, and the testing of existing expoeure control methods for adequacy of preclslon. Fluctuations of about f 1% exlet in the existing exposuremmtrol ult. "heee m e regarded serious for intercamparison purposes, so a new unit baa been deeimed and the priaciple of operation tested with available canponents. Since the test is satisfactory, suitable components are be- ordered for the final, working model. tially 8 Tawneend balance circuit in whlch the desired cxpoeure can be preset, and which d s o displays radiation rate. Preparations completed for t h l e Intercamparison include the con-

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The Victoreen condenser r-meter continues t o receive attention of two The first is a monthly check of voltage sensitivity and thimble rehis m s started in 1956 and is expected t o continue indefinitely. The second relates t o the use of the thimble chambers in ph&aS. presence of the thimble changes the r W o Q flux which would have been present at the center of the thimble in the intact phantom and thus gives a false reading of exposure dose. Correction factors have been determined for some x-ray qualities in the conventiondl range and are found t o depend on the x-ray quality, on the f i e l d size, on the depth in the phantom at which the measurements are made, and on the size of thimble used. sirable t o extend the scope of these measurements before mak hg a complete report of the findinge. large as 30% may be applicable under certain circlrmetances. There are indications, however, that corrections as Several years ago measurements were made in a rough way,good only as t o order of magnitude, on the neutron flux to which operating personnel and t o which the patients would be exposed as a result of operation of the synindeed, and that the neutron dose received by the patient vas essentially inappreciable compared vith the x-ray dose. These Indicated that operating personnel were very ve ll protected Recently It was decided t o undertake a man reflned measurement sequence of the neutron dose received by patients under typical circumstances. A neutron howitzer has been constructed for saw relative measurements around the synchrotron The method of H u r s t &&. (Rev. Sci. Instr. 27: 153-136, 1956) using fission f o i l s - and phospharus instead of sulfur -w i l l be used t o estimate the neutron spectnun. A standard Po-& neutron source is available t o calibrate various parts of the experiment. A substantial number of runs have been made v i t h the havitzer, using rhodium foils, and also uith the phosphorus. are not yet available t o us, so it has not been'possible t o cmplete the The rrquisite fission foils Permonnal oi this section ai course operate tht synchrotron for each exposure req- In the treatment of patients. ment planning, make the required molds and boluses, and manufacture a variety of useful appliances . They also assist in treatThe chief of this section is involved in the teaching of rsdiatlon physics, primarily t o residents In Radiology, and in the affalrs of several

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The physics Section is under the eupcrvision of I)r. (lail D. Adam. Operation, maintenance, and developrent of the synchrotron M carried such molds and moulages as may be required for each patient t of a cut ate the agreed treatment plan. Miss Mary Lauise Meurk haa undertaken the treatment p2anning for patients in collaboration vlth the Cud Radiology Section and also Is working on the "quick-ch.9a& aperture rryetern with the new autamtlc isodose plotter. Miss Ilga Riekatinm is curnntly working on the neutron problem …