The Therapeutic Use of Radioactivew Elements in Malignancy

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L'Xtosn months. Althoughr the total number o f oams i s aomgaratively mmll and

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f-;bsosarcor:.s of l i v s r , 1; adenocarcinow of livzr, I; cercinom of coecum with metas- -mtirtaszz, L. 12 all exceipt nixof the casea, diagnosis was confirmed by tissue biopsy 6,’ ztem-d aspiration of bone marrow. O f the total numbas of cases, 35 are etill living, ~ l n d33 are Bead. Post-mortem examination was performd in 22 oaeee. 2: Itl : fm i liar chemical ma biological bahavlor, its short half-life (6.5 days), its suitable radiation qx~ctrum, Find its eaee of production in a cyclotron i n the It was prepare6 by d mter on boEbardmnt of chromium i n the The mawanesea together wiag asir - p r cent gelatine solution 88 the supporting colloid and vehloler The mdboactfvity of the prepared sol was determined by masurine the gamna ray Inix3man tms calibrated aitha standard ample of radioactive h-zanem, supplied th n ugh the courtesy of the Miass~hUaettts Inatltute of Technology, Radioactivity The initial act1t;ity of the freshly prennmd colloid ueuallg varisd between It m a almst lovarfoblg ahinLstered ~iti-ihtm?lve hours atter preparation. Then the products of the Atomlc Til3atOak Ridge becam3 available for x een rak ?urpom8, in,Aq;uet, 1946, E corcplete conversion t o the t be mpu tic Uof colloidal radioactim gold (Aul”) was eff eo bd. i ~ z ~ n n - ~.i.:f‘;h arn in hd Itsas from decay t n transit. This was done for various reaeona, Theae advantame, tomtber wlth

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II. Absorption Rnd Distribution of Colloidal Radioactin k;angan9m and Cold in the Eody. Go=-eut: The rate of dimpnearance was detorninod 5y t h e following xmthod: vsin. f;:r 7anderbFlt Units of radioactive gold were then injected into the l e f t

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anteoubitsl win. Two minutas later,tho first 2 cc. blood ampla r0mved from tb r i g h t mtscub1tc.l vein, end this vas repeetee. at two minute intervals during the 111. Comparative Distribution i n Body Tissues o f Colloidal bmganese and Colloidal &ld. s is tri but ion studies were csrried out by measuring the radloactipity o f tissue rj?::.-lc.: obtaifr-ed fit autopsy. L-ftor careful mighing and processing, radioactivity raas:?~-’?ntsmm rade Kith a thin xica window bell-type Geiger-Muller oounter, A L w - - wza o siguificant difference in tho distribution of the In th b d y tissue^, as indicated in Tables 1 and 2. In tb oatso o r xa8nganeee, a C - ; .SAZCz ~ l yhigh activity was found in the panareae, although the maeon for thie L- K-.S ex: cted, chereao the rel ~ tiv euativity o f gola i n the spleen via8 oonsiderably

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o f Colloidal Emgtineae and Colloidal Cold of tissue, mlnted t o the heart~nusclea8 unity). In two eases zleaults are eqreased in counts p e r minute per @an of tiesue reihtve t o heart mueale teen a6 unity. Xn the third case concentration i n mlcmgrana par grm. of tissue a m given and es tim tes of tb total fraction of the Initial dose in o ert nio orgrins are oalcu.latzC. - kc t iv it y Activity Activity Concentration mated trac-

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'3%m lect ion 01: thew sixty-elght patients for tre a tmnt was baaed on no rlzid eri ler is. EL:izz:t kh da of moplaeltic disease es posaible, i n an attempt t o determine thorn byFcs IEnhich therapy wafi vast effective. However, as the study pmgresesd, I t soon h3ce.m appa%nt that the most satisfactory result3 were t o bo obtained ln chronio I 3 ~ c.3 ,o ur attention waa increasingly focuasd on this group of fat i ents, to fbe gradual sxclcsion of the o tbe rs. I n the early stages of' the vioIQr;, an effort was made t o treat as many Although the figures i n Tahle 3 are not statistically significant, it will tx s33n that the probability o r msponse to im top tbm py mas apparently not altered achie - a d in tho group of patients who had previously received X-radiation. The c ~ i ? ff actors to b considerod i n determining tk lilarrllhood of ref¶pOn80 in the Individual pntient were, ( a ) the s t q e of the disease st which tmatnr,nt and { b f shother the ~ IV WE IE was of tb acute o r chronic variety. g t . - ? * b h cnndtdtitos f o r therapy ware those patients in vhon ths dlaeaae wan chronia EL. ,Ln came under observation in a relatively esrl;. &a@ of their Illnene, uhereas th 13wt eatlefaatory rersults mm t o be axpecied i n t h acute ~ ~ 6 8 8 ,traated in

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Cbnaral haly a i a of Clinical Resulte Previoue h0. Of Improved $ Implove d Subacute monocytic leulamia -

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In over two 13~~61x16intravenouer injection e of colloidal raCioactive raagt:i‘r3t33 and rn dio active gold, only two inmediate reactions mre encountered, b3th of t h 3 m oucurring i n the sn239 individual. The patient waa a thirteen .I %,‘1,I,, olc, Khdte rnnle, (Patient8 ir, Table 4). In each instance the Isotope ssv z ra, ahaxing ohill followed sfaortly by a repM rise in temperature t o 104- :zsts :or mnsitivity t o gelatine, the mhicle umd in the preparation of the colloid, mra nagative. It was therefore lmpossibls t o ascribe the mactions b;Ithh a fer d nute s after the Injection, there was a Tbeee symptcms persistljd f o r The pnllont gam no hiatory of‘ allergic p30nomena and &in I n none of tbe patiente was anything compareble to so-called wradiation s~c’rin8ss’’ encountered. Ayproximately ten per cent aomplolned of a very m i l d Cagrea of nausea which usually pr sls ted for four or five days, but in no b8tanoe . r e. this wvem enough to prevent an adequate diet aq inteke, On a feu occasionu, .tk undiluted sol was injected too rapidly, the patients colrplained of a .,t;i~;it,t u r n i n g sensriticn in the nree, but this diaappared within 6 ?%vi wconda - r a -t..-.-.~ z k rate of injection NRS slomed. The Ellmost t o t a l lack of any toric symptoms following the injection was o f - - nci ds rcS k economic advantage t o the patienta, in a mah ae they were able to = at. Tho= -wtients who were in satisfactory cli nio al condition =re i oU oss d -Analysla of the Remits ObtRined In the Tmatmnt of Rodgkin’s Dlmaee A total of ae,ventean Ft i ents vdth Hod@Ein*8 Disease were treated in thir 1 * . Id L.t.bJ .< -. I n each inatanae the diagnosis was eat ab ll shed by tissue biopey before

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- therapy wag undartajren, KO t3peciriu critaria m18 employed i n the aaleotion o r caws, hence a opportunity was afforded t o obaervrrre the effect of treatmnt under ava ~ i r ? t yof condStioaa. W essential bta on them patianta ie given -33 &.nation of eymptpma before radioactive tharapy was e t & r t e d ranged - - - > tiant vcrisd betsleen thirteen and one hundretl and seventeen millicuries, lP-9 87er3~5 dosage administered at any BfnrJe tzwutmnt, f o r both isotopes, 7;m tibout sixteen unitis. The averam internal betmen trecitmnts vas s i x woke. :'.r:tiant 5, on Table 4, received the largeet to tel do sap of raclioaative material, 7016 overa fourteen-raconth prlod. This patient's oaae history l e given i n t e e n of tb seventsen pGtlents, them being no apprecieble msponsa i n the rem b i z s four. Oil the eight patients who showed the ms%marked improvement, five kr-l rsczivad previous X-ray t met mm t, and ell had shorn som deme of reqmnmr In grading ths degree o r inprovemnt In each of them patients, (Table 4), 2 mu@ m2irIc scoring system waa devised, bamd on thaa objective findings; (1; "oight gain, (2) Eteduction of fever, a n d ( 3 ) Reduction of hepatomegaly, s?3.sncxsgsly, or any palpable tumor masi. Eaoh of them finding6 mi8 worth a Syrqtonatic lxrtpovemnt, when it co-exlsted Kith one or mm o f However eymptomtlc responm

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Xban first men, I n July, 1946, this 40 year o l d white female gave a T=h2 x-ed blood count was 4.17 million, white blood count 24,500, and hamglobin E ~ s . The diff are nti al picture was wlthin normal limits, except for a A. > t k rmrked 2rsgonderanca of polymorphonuclear cells. During the ensuing o r z,",ich ti- the red blood count uaa 3.82 million, white blood count 4,850, XISS ab-ain to a level of 3600. During the following m n t h she vaa given four Se?tember, her blood glc tur s shewed a red blood count of 3.16 million, hem- [ J o b i n 10.5 m. and white blood count 9,320. o c Sspter&sr 17, 1946, Bhe remi ved an additional eighteen millicuries oil MLl Shortly before leaving the hospital Two ani E\ h : d f vieeks after her return home her local phyeician reported her hca1 hospital with a temporary riw I n tb white blood Gel1 level, HOW -

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together with unorsxla and oooarsional nausea and vom lt bg. Chen a b returmd t o the hos9fW am nth lat or ahe waB cirxtmmly weak and cacheatia, mdit e,; obvious that hsr diseaes was terminal, The red blodd count wee 2.08 million, . a ~ czr. ~ zof any platelets, Several blood transfusions fall ed to effect any ir=_::.iavsrentIn the blood oytology a n d the patient expired on Deoember U., 1946, Cozlnent: This oars illustrates the difficulties encountered in our fittem2ts t o tmat Hodgkin's Disease i n the terminal stage. Although this pti ent to ler at a dra a i ation fairly well hen treatrrsnt was first inetituted, a8 the dlmasts Cn the other bund, P a t t n t 2 in Table 4 was tlleatod at 8n 6arlbr atagg ofthe Cisease, sithR far mre satisfactory result. Case Eiatory (Patiect 6, Table 4) This 28 year old, white m a l a wa8 admitted t o Vanderbilt wepita1 on r:Jcths' duration. Exslminatfon on admission revealed aell - develop d and fairly 7911-nourished, ratbr pallid, white male who ap-wamd chronically ill. There yFas E r;.,ild degrea of lynqhadenopathy in tbe cervioal find epitrodhlsar mgione cs:: o x mall node nais pelpable in the le$$ axilla. no other positive physical fl nd lng e ware noted. The red blood count WIIB 3075 million with a hsmoglobln of

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on tin ly cfsbrile tm moks after tb rap y. Be left tb hospital in good condition on D3cen,rhbsr 13* 1845, a n d conthued t o do -11 during t b emuing three weeks, pinin ; A to tid of fifty pounds during the sfx-aoek period follow i ~therapy. Them xa8 considarable syqtomatiC improvement, and the patient became s h w d 8 ssd blood count o f 4.47 million with a bemoglobln level of 12.0 @a, nii li curies of En . On Jmue.ry 22, 1946, the patient received an additional 11.6 Them bouts lasted for only ax ith tb temp ra turn never rising above 10Z.Oo, rky or two and the patient was able t o aontlnue working mgularly at hie job. (211 Karch W ,1946, he miturned to the ho q pital and m cel ved 10 milli2uurles of . On A p r i l 16, an additional X3.0 nslllicuriee of l?.u52 was given.I.& 32 On cisy 8, 1846, the -mtient wa8mab it ted to the hospital with aomplaints 1 : lon.ct iv smg an ese wu.3 not available a t this tim, and the patient uas tbsrefore

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4.; million, hsr&&obFr! 855, and white blood count o f 6,500. Lx;'--vdimus fnjeations of mvan milligrams each. His blood picture a t that tha shopped n red blood count of Shortly after returning horn Z cl liv 400 and nunemu6 pte chia e and ecchymtlu area8 appeared in the akin, toge-chc: cplt3 bleeding and infection of the m. After three blood transfusions, tt wits blood count returned to 6,000, the r e d blood count t o 4.0 million and Eowsver, after the second injection, the Rhib blood aownt Durinc the next six xeeks the gtitiont felt fairly well and 88s able t o r-7 slrL.thu & them waa a doily te q era ture elevation t o 1O2.Oo, Ha XeCeiVed l?cxr?iiaions at intervals, t o offset th persistent anemia. czakr ~ s ~g rad ally kc me nore maxkeii, end on November 21, 1946, the patlent However, fever and Cnt hi a admission lie appeared t o be In n?Lczr 73s palpable 6.0 cr.3. below the cost al margin and the liver edge 4.0 ne. ca:~': 5,450. %d if few nti ol blood picture remalmd as sect i ally nod. The patient Ka:3 Given o. total of' five blood tram fusions during this addas i ori, together with 22.0 units of colloidal radioactive ~ 1 don Morember 27, 1 5 4 5 , %'ol;Lowed by 19.0 writs on I2/4/48, b - cme afebrile, and there vas considerable reduction In tho alze of ths eyleen EIIG 211 lymph nodes. bb or u tory studies on I>ecenbr 7 , 1946, Shomd: RBCDurlng this internal the patient

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b;.lc.;c! tr?-?2uBLon8, I;&o;hite blood count gradually fell, reaahfng a level of -:w dcux - y6, 1047, and the platelets, 88 o b ~ ame dIn blood gmeara, beem T:::~ This pat isnt is still undar obssrvatioo n t tbe present ti-. Corrmnt: Thio pti ent 6homd a very atri king ma?onee to therapy ahsn The blood cgtology was not unfavorably altered by treatment, i3?;t3O E the other hcind, there m8 an actual. incmaae I n the red blood count Individual Variation In Response t o Therapy hl tb ugh it i~ apparent from the above that, i n anyr given patient, tb chmces of obtaining n sctisfactory response t o thera3y were &mater i n tb ev lier st & ges Gi' the die ease, tb factor of individual vnriation mndors It '--,:!c?csible to gret ict the result or tmntmnt i n an individual patient. Thus our til? u v e r a p duration of the dleoose before therapy mi6 undertaken was 14.4 months; ch?ycs is1 thr-t group i n which the results were poorest tho duration of the ilin-.ss 68s only 13.5 mfitha. The u v e r q p a ~ oof tho former group wa8 35 years, ,m5. o f tb latter 37 yenrc, in dim tin6thqt thle was note factor. Analysis of the Results Obtained in the Treatment of Chronic Lymphatic bugtenin

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rTiney wsre under observation for variable perioda of time, ranging from tw aeks and a half? units, aud the interval between treatments about seven weeks. The c3matiL.1 data on them …