Letter to H R Blieden, Subject: Analytic Efforts at Oak Ridge National Laboratory and University of Nebraska

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Advanced Teclxology Apslications Our t);oushts on the relationship betwen the analflic efforts being ntFported Cancer'' and other naticnal cancer radiotherclpy programs are given below. The analpit efforts consist of independent krt complementary programs at the Oak Ridge National Laboratory and a t the University of Rebrash. The work at is yrimrily directed a+, the study of the transport through mtter (fer example, tissue and bone) of those particles that have been slJggested t o hprove cancer radiotherapy, i.e., neutrons, protons, negatively charged pioRS, e and high-energy heavy ions. The ultimate purpose of the O R U pmgram is to proviile calciilatio;ldlly the kind, energy, angle, and spatial distribution of all the particles hkich are produced \zhen any of the particles of interest arc incident on tissue. Frcm t h i s infonution, quantities of interest, such as absor5d dose and LET spectra, may be obtained. "Se University of Nebreska's program is primarily directed at providing theoretical e e l s of particle dstectlon and cell sunrival vhich may be used t o predict t\e relation between the readings of radiaticn-detection instmats and the te bvi or of biolosical matter in response t o that radiation. The infomation on the particle spectra as a function of position, which will be provided by the OFSL program, is precisely the information that is needed as input t o the models being developed a t the University of Nebraska, and thus the programs are t m l y conplementary. Indeed, sane calculations have already been made both at Nebraska and z t @!CL in which each group has applied the other's results. n\e programs a t the Oak Ridge National Laboratory and at the University of Nebrash are txll developed s h c e they have k e n supported by the U. S. Atonic Energy Cmdssion (and by the National Aeronautics and space Administratian in the case of OR\% and the .Xational Science Foundation in the case of the University of Xebrash) fcr apj9ication to problem other for m y years. The computcr codes that have been developed a t OR\% can be used t o provide useful infomation at the present tim. FOT exanple, calcdations a t the request of R. Hutson of Los Alamos Scientific Laboratory are i i progress t o detemine the extent t o h-hich the presence of bone embeddecl in tissue will affect the use of negativcly charged pions hi radiotherapy. Cal ~ ~ l3ti01 ~a t BEST COPY AVAILABLE COP,ED FOR

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+& request of C. Richm of LASL are also in progress t o detennine the extent t o which silicon and gem i um detectors m y be used too b tah dosimetv information in the vicinity of a stopping negative-pion beam. only a first atterqt a t understanding thc coarrplex dosh-try problems bwch will exist hhen negative-pion beam are used for radiotherapy. Ultimately, it will be necessary to s - d y many detector systms and d e many cq aris an s between calculated and e.xperimenta1 results before the dosimetry problem is well d s r - stood. In tkis regard, it shcr;ld be ncited that the theoretical models being developed a t the University of Kebraska are applicable t o a large variety of detector systems and w i l l , therefore, be invaluable in cawing jut these studies. It is anticipated that additional requests for information from the group a t WSL w i l l be received as their program develops and it is expected, t5at the calculated results will aid ccnsideret?ly i n understanding the exi>erznental reStanford University (H. Kaplan, A. Wwetman, and D. Boyd) and a t the 3ritish Columbia Cancer Institute (H. Batho), who are interested in the use of negative pions in cancer radio+,erapy, have not as yet directly requested calculatimal support, but they are aware of the analytic programs and w i l l be fully infonrd of the results as they &me availa'cie. tained will aid than in developing their programs and that their caatments will enable us t o provide needed additionai information. The validity of the calculated results nut be verified by caqmrisons with exper h ntz l data. A t the present time, experimental data taken with incident pion beams are very limited and will presumably remain so until results from LASL become available. For several years, the health physics group ar OR% (bko are partici ating in the analytic studies) have been engaged in a coll&orative program ~54the health physics group a t mTwho have available a pion beam, and through this mechanism some experinental data w i t h which t o verify the calculations h v e been obtained. m s collaboration is continuing, and it may be possible by this means to obtain addition21 verification of the pion-transport This is, of course, It is t o be hoped that the results obThe calculations pertaining t o the use of protans in cancer radiotherapy, bhich Kill be carried out as part of the analytic programs, w i l l be of direct interest t o the ihrvard hlwrsity radiotherdpy project that is being suppcrted as part of the RXSN program "Advanced Instnrmentatior, for the Diagnosis of Cancer." The calculations a t ORYX., and a t the University of Nebra$ca and the experimental prog ~ a mat Harvard are not closely correlated at the present time, but A. Koehler of Harvard is mare of the analytic program and has expressed a desi% to obtain e.rcperimenta1 data with hliich t o verify the calculations, so colla~oration between the projects as they develop may be anticipated.

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The calculations pertaining t o die use of neutrons in radiotherapy, which w i l l be carried out as part of the analytic programs, k i l l be of direct interest to the radiotherapy prograns a t the Naval Research Laboratory, at the bf. D. Anderson Hospital, ar,d zt the University of liashington. Because the hXL pmgran w i l l use higher neutron energies than w i l l the other installations, the group a t h3L are more in need of the type of calculations that can be perfomed a t GR\L, and therefore, ir it i ally at least, calculations most pert-bent t o the Kill be Perfom.&. The Nu. pram Ip.. Theu and F. Attix ' l have carried cct a variety bf experimntal neasiirenkts ~ h i c hw i l l be very useful iq veriF,-ing *.e calculations. iuso, P. Todd cf Pennsylvania State University is i n the prccess of 0btainir.g cell-survival data in aphtm using the h i collimator and neutrm bean. Cqzrisons witk these data when they become available W i l l be of UKwest sigrificarxe s k c e they will prcvide the first experhentnl verificatior, of the rerilts cbtamed by combining the transport calculations from ORhZ and the cell-survival theory frcm the University of Xebraska, data, siiilar t o those being obtained by P. Todd, w i l l be obtained by M. Raju with the pion beam at LAiPF. Comparisons of the calculated results w i t h these experimental data h i l i be made as soon as the data are available.) The existing c q t e r codes are capable of carrying out the calculaticns described above, but in;provm.ents in the codes are both necessary and desirable, so a substantial portion of the vldlytic program a t OFWL will be devoted t o making such hprovments. In addition toa continuing effort t o i?corporate ktc5e c31cdlations the latest and best available differential cross-section data, work is iii progress to include range strGggling i n the charged-particle transport calculations t o develop a subroutine that will incorporate the University of !kbraska's theory of track structure into the calculations and t o develop a subroutine that w i l l resent the calculated res7llts in the fonn of isodata cofitours which, it is Accurate calculations pertaining t o the use of high-energy heavy-ian beams in cancer radiotherapy cannot be pcrfonred at the present tinr because of the lack collisions. Same infonnation can De obtained by simply neglecting all nuclearreaction products, and calculations in this approximation have been performed a t the University of Xebras'u ard elsethere. Work is presently in progress a t ' the University of Xebraska t o obtain calculated results in this approximation for comparison with the experkzntal data from heavy-ion beams which have been ant! are being taken a t the Donner Laboratory. Dcfinitive calculations, however, be possible only &en the prcdxction and transpofi of IIYclear-reaction produets can be included, and tkerefcre a portion of the ORhZ progrm. is being directed a t develoTiri a theoretical model which will provide the needed differthougRt, w i l l be of most use in radiotherapy.

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I t seem dear that *.e analytic program outlined above w i l l pzwide mLIch useful information on the qplication of neutrons, pmt?, negative pions, and high-energy hemy ions to cancer radiotherapy. It is equally clear, h w - ever, that t o be most useful the anallztic programs must be closely correlated kith the experimental preclinical radiotherapy prcgrans, and therefore every effort w i l l be made t o ensure this correlation. Ultimateiy, it is hoped that results obtained from the analytic program will make it possible for radiotherapists to translate their clinical experience b i t h photons to the new radiation mdalities with the fewest possible der of surprises. k soci ate Director Vice chairman Neutron Physics Division Oak Ridge National Laboratory Behlen Laboratory of pllrsics The University of Nebraska-Lincoln