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-- Srtb-tark Title; The Effect of Total B o d y frtadlation on bnmunolq Tolerance of bone Matrowand Homografts of Otht Directing Agency: DASA Coatmetort Baylor University College of Medicine Project Offtcert LCDR Richard Gawer, USN Project Coordinator and - Baylor Univerrity College of Medicine Ch e e ~ ica tba tUnciaa a i flad Report Period! Feb. 1, 1962 - Jan, 31, 1963 (Reptodoction In whale or in part La petmltted for m y pwposc of t h +
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T h e primary purporc of this investigation is to define and quantitat the efl ttt a of total body irrrdirtion, T h t fundamental problem of phyrlcrl dosimetry ir that a simple nYmerical expression of done i s inadequate to describe the distribution ' .ntcnrity and quality of radiation delivered throughout the body. W h i l e striving to achieve uniformity of distribution in order to allow I meanin and repreducible rtrtement of dome, it ir recognized that any radiation , exporure received under other thrn controlled conditions, is apt to be a partial body exposure, likely to be of unknown geometry, and certain to be of uneven distribution throughout the body. The biologic component of irrrdiation dosimetry has these factors, 1. The observed biologic r c ~ ponsc ra r e not specific for irr8diation 2, hlcchanisrns of compensation and repair obscure the direct effect of 3, Such nrrchanirmr are themrclvcr sensitive to continued irradiation an recognized i n the concept of a time-dose relationship 4, Uncertain and uneven distribution of radiation throughout the body must have uncertain and inconstant effects o n repairative reserve 5. Such reserver are peculiar to the individual and influenced by ate, current state of health and pYior i h e s s or injury porribly unrecogni: T h e complcxitier are seen more clearly with increasing knowledee bot the complexity of the problem itself ir not increased. Some perspec in rttx#ying the problem 1 1 gained from recogniting that irradiation tan k used clinically with acceptable rdety and affettivencrs. Man7 approaches to the problem have been undertaken, and reviewec fat thin report. Major ntudkr which have been completed and reported prevlourly are lirrted, and the continuing rtudy of clinical observations 01 pmticntr receiving therapeutic total body irradiation Is summarized. Detailr of investigatLonr carried out over t h e paet year follow the swnrn, A total of 110 patientr have received thcmpeutic total body irradiatic - On-cmach pattent, follow-up is continued as longr a s possible so that effect . of irradiation may be observed and recorded, A11 patients were sufferinj from generalized direare: becrurc many w e r e approaching the terminal stage at the time of treatment, long term obrervationr were limited. l n bappeared, impending obrtruction war rclkvcd, and n few bedridden rt k ntr became ambulatory, While long term8 control of dinseminatcd ricer cannot be expcctcd with nny method of treatment, rurvivals up to 9 - 10 ytsra fallowing rrporurc dwnonfittntc that rnodcratc amounts of t c body irradiation c a n be tolpratcd without dangerous rrrquclfic.
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A t the beginning of the study, it waa planned to collcct two ~ t ; c s of pattents for comparhon of r ~ ~ ponae, - o n erccciving aingic do?tcq o aerier inclodcr a larger number of patients than the protracted expos. g-rsp because, for many paticntt, plans for protracted cxposure cod < not be carried out. In some cases the desired therapeutic effect was obtained with the first expoaure and protracted irradiation was not indicated; in others, further irradiation was contta- indicated because of paor general condition. Among the latter group are pat k str who, having m a the gamut of all other forms of treatment, are referred fot irradiation as a tart resort, In addition to the two series, third group evolved during the cou with good response but who, after periods varying from 3 to 29 month c of stmdy. Thir is represented by patientllr who received protracted c x l Q developed rymptomr rcquirine additional total body irradiation, in80 three categorierr 1) ainile exposurer ranging from t S r Z8 protracted crporurtr raniina from 2 5 t - 400r over periods of I to L3d.y.. and 3) repeated protracted expowarea ranging from )Or - 250 1 e? cmmrae 4 2 - 4 cootrrea) over pertach of 5 to 42 months. Thr quml of patients i n each eate~ory,with range of etposurc and elapsed time, mhown in Table 1. Accordingly, for the present r tv it w, the paticntcr have been divide
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No, of Ptr, Time Btcamse expression of dost requires a statement of time, and prtientr received more than one COU ~ SC, the amount of irradiatiea ?ed in each cour8t for crck patient 48 outlined in Table 3.
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,' Although systemic effects of radiation, w e r e recognized anti rcportcd a s early a s 1897, there is still no satisfactory explanation for the set of T' biochemical changes. noted clinically and experimentally, that account bwr "radiation sickness." According to h i s report, symptoms develop "most commonly after total body irradiation," and i n partial body irradiation, the incidence and severity of symptoms depend upon the anatomical area exposed. T h e present series has been investigated with relation to protraction of exposure, to amount of radiation in single exposures and, during the last year, by physiologic studies before, during and after total body irradiation, For purposes of evaluation, the severity of symptoms has been graded as follows: 0 3 = nausea and vomiting one day, and 4 = nausea and vomiting more than one day. Two patients were omitted from this study; one patient, tcrminr at time of treatment, died within 24 hours and one, an out-patient with concurrent tuberculosis, was lost to follow-up. Table 4 summarizes the none, 1 II anorexia only, 2 = nausea only, +One patient with Grade 2 and one patient with Grade 3 symptomr had nausea and vomiting prior to irradiation.., The table indicate8 that a total of 21 patients (19%) had symptoms varyfng from mild to severe. While this figure is not high, it cannot be accepted without reBervations for several reasons: 1) any or all symptoms could be due to cancer and/or its complications, 2 ) two patients had symptoms prior to irradiation exposure and 3) no explanation is provided for the 87 patients (817.1 who developed no symptomr at all.
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I . In evaluating radiation sickness according to amount of irradiation, Category I is used because response to a single exposure is easily recognized and symptoms are not complicated by the .cumulative effect repeated exposures. Table 5 shows the number of patients developin mptoms according to amount of irradiation Idlowing a sirrglc exposur No. of Patients Grade had nausea and vomiting prior to irradiation. Y<? Study of Table 5 shows that, for-this group, radiation sickness $dlorlng single exposures up to 200r is negligible except for the putrlin incidence following 50r. This is particularly interesting i n view of the 53 patients who developed no symptoms,--48 of whom received equal or greater amounts of irradiation. For this reason, the histories of these 5 patients were reviewed. The first patient had widespread metastases with possible involveme of gastrointestinal tract from carcinoma of breast. She was terminal at the t i m e of treatment, requiring narcotics for pain. Nausea and vomiting occurred following irradiation but symptoms could have been caused by motion and manipulation, by medication, or by disease. -The patient died 1s days following treatment. Histories of the remaining 4 patients are particularly pertinent. All were occupants of the same ward at the same time. The first to receive total body irradiation had carcinoma of kidney with metastases to liver; k was receiving partial body irradiation over the abdomen at the time of tal body exposure and h i s condition was complicated by a gastric ulcer. *here was no vomiting but h e complained of nausea following trcatmvrt \ d t h i s was noted and discussed by his fellow patients. The remaining three patients received total body irradiation w h i l e undergoing a course of radiotherttpy for testicular canccr; ah do ml nal
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receive total body irradiation complained of nausea and though VornitiqpjTanticipated, it dod not occur. The last two patients (R.hl. and G.M.) develc nausea and vomiting during partial body irradiation and received supportis tre lent which controlled the symptoms, Both patients received total t o t irrr - ration on the same day and both developed nausea and vomiting s00n.a t( mtment. T h e r e is no question concerning the validity of symptoms in th men; both w e r e genuinely ill and both received specific medication for con of nausea and vomiting. Both w e r e well enough to continue partial body ir: diatton and their courses were completed without interruption. These circ stances indicate that in a t least three patients, nausea and vomiting was an cipated and the power of suggestion m a y have played a significant role i n +&c.Of the S patients who developed nausea and vomiting following exposur of 200r - 250r, two had symptoms prior to irradiation, two had primary ca of the stomach and were receiving partial body irradiation to abdominal fit and one, with Hodgkin's disease, had extensive involvement of stomach and The component features of radiation sickness,--anorexia, nausea, vow and fatigut,--are particularly susceptible to augmentation o r control by el, of motivation or suggestion. It i8 well established that a patient may have the symptoms of radiation sickness after being placed in the radiotherapy . e.* 3 without turning o n the x-ray machine. 4 jthcr, whether speaking of total body'or partial body irradiation, may be adequately explained on a basis of the attitude and experience of the ptofts; pcrronncl and personal acquaintances in contact with the patient. O n t h i s basis it is the firm impression that at levels of total body cxpc below 200r in a single exposure, or i n protracted exposures up to o n e rnont there need be no incapacitation due to radiation skk ner s. T h e problem could be eliminated by selection of stable individuals, by education and sound information, and by due attention to motivation and The difference in incidence of radiation sickness from one center to haustion when the ill-prepared and uninformed individual is exposed to the suggestion that he h a s been exposed and that sickness is inevitable. Conversely, the symptoms will be induced by panic, exertion and cxc Therapeutic total body irradiation is offered in cases of disseminated cancer with the intent of relieving symptoms; a t the same time, other c f k c of irradiation m a y be observed. while certain types of cancers are consrd radioresistant, there, among these individuai cancers that may bc raclioponsive. Since these cancers cannot be identified, the practice of with - Ldng referral or treatment may lose many opportunities to help p nt iv nts a( to collect information. The lymphoma group i s recognizcd a s btning arr thc most radiosensitive cancers and analysis according t o di;igrio\is wn4
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niurca and vomiting during partial body .irradiation and received ruppo treatment which controlled the ryrnptomr, Both patierrtr received total ’ -adiation on the ~ a m cday and both developed nausea and vomiting 5OL ;atmento There is no qucrtion concerning the validity of symptomr i r I men; both w e r e genuinely ill and both received specific medication for 4 of nausea and vomiting. Both w e r e well enough to continue partial body diation and their courses were completed without interruption. These c stances indicate that i n at least three patientr, nausea and vomiting was cipated and the power of suggestion m a y have played a significant role i Of the 5 patients who developed nausea and vomiting following cxpo of ZOOr - 25Or, two had ayrnptoms prior to irradiation, two had primary of the stomach and were receiving partial body irradiation to abdominal and one, with Hodgkin’s disease, had extensive involvement of stomach The component features of radiation sickness,- -anorexia, nausea, i and fatigue,--are particularly susceptible to augmentation or control by of motivation or suggestion. It is well established that a patient m a y ha the symptoms of radiation sickness after being placed i n the radiothcra. even without turning on the x-ray machine, The difference in incidence of radiation sickness from one center t q. nothcr, wh c th tr speaking of total body or partial body irradiation, may. (* adequately explained on a basis of the attitude and experience of the pro personnel and personal acquaintances in contact with the patient, On this basis it is the firm impression that at levels of total body e below 2OOr in a single exposure, or in protracted exposures up to o n e n t h e r e need be no incapacitation due to radiation sickness. The problem could be eliminated by selection of stable individuals, education and Bound information, and by due attention to motivation and Conversely, the symptoms will be induced by panic, exertion and e) haustion when the ill-prepared and uninformed individual i s cxposcd to I suggestion that he has been exposed and that sickness is inevitable. Therapeutic total body irradiatitrn is offcrcd i n cases O C disscrninnt cancer with the intent of rclievfng symptoms: a t the samc time, other CI’ of irradiation may be observed, While certain typss of cancers are con radioresistant, there, among these individunl cancers that may \)c radio responsive. Since th csc cancers cannot bc identified, the practicc of wi potding referral or trentmrnt may losc many opportunities to hell' 1iatit> And to collect information, Thc lymphoma g r o u p is rccogni7.c-d n.; tlc-inc hc most radiosensitive cancers and annlysiq according to cii;tgrttJ<is w a * carried out to dcterrninc if thi a group rcprcsentcd thc majority of tttvh ’
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Diag no si s C at ego rie s Total Ca, of lung Head t Neck cancer (larynx, face, tongue, etc. Ca. of colon & rectum Cancer of stomach Cancer of pancreas Malignant me la noma cA~'liycr, kidney, prostate, etc.) The lymphoma group (leukemia, lymphosarcoma and Hodgkin's di is represented by 41 (37%) of t h e 110 patiantr. Of the 14 patients .rho received total body irradiation for Ieukemta, 3 w e r e terminal at the ti of treatment and died of disease within 3 months; one patient with a c t t tuberculosis war lost to follow-up. T h e remaining 10 patients had cor riderable r e h f of symptoms with survivals ranging from 6 to 4 6 rmnr Two of there a r e still living: one (No, 91) received 250r/14 days in February 1959 and ham been observed for 35 months; t h e second ( 1 0 9 ) received 150r ina 8ingle e%posurc;and …
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