HIGH LET RADIATION THERAPY

The High LET Radiation Therapy program area is still in its formative stages since the worldwide interest in the use of high LET radiation for cancer radiotherapy has been developing only during the past few years in selected laboratories in only two or three countries. The development of high LET radiation research commenced only since 1970 when both American and Japanese scientists became interested in high LET radiation and its possible use in radiation therapy. With the high cost of equipment, facilities and operations, there is a great need for international cooperation and collaboration for further development of high LET radiation therapy. There is also a dire need for unified protocols for therapy, standardization and dosimetry.
The initial meeting of the U.S.-Japan High LET Radiation Therapy program coordinators and their committees was held in Tokyo, July 1975. The purpose of the meeting was to evaluate and coordinate the interests of each group with respect to: 1) development of equipment and machinery necessary for producing high LET radiation; 2) preclinical physical and radiobiological measurements necessary before clinical trials can be initiated; 3) preparation for clinical trials; and 4) determination of areas in which cooperation and exchange of information and scientists would be advantageous.
Because of the urgency of the neutron problem, the initial meeting between Japanese and Americans was largely limited to a consideration of the various preclinical and clinical aspects of neutron radiation therapy. Considerations of other heavy particle and high LET radiations will be dealt with in future meetings.
The participants of the July 1975 meeting consisted of scientists, representing physics, radiobiology and radiation therapy. Subject matters were divided into five general areas.

1. a description of the present commitment to high LET radiation therapy within each country.
   
2. a review of the available neutron beam therapy equipment, including considerations of the state of development of shielding, collimating, and dosimetry.
   
3. a summarization of the basic radiation biology and the state of biologic dosimetry with neutrons.
   
4. an assessment of the present status and plans for development of clinical trial protocols.
   
5. a review of radiotherapy with neutrons from ²⁵²Cf.
   

At the present time, there are two fast neutron gnerators, both cyclotrons, installed and nearing readiness for clinical application in Japan: the Institute of Medical Science (IMS) cyclotron (Cyclotron Corporation, Berkeley) and the National Institutes of Radiological Sciences (NIRS) cyclotron.
The U.S. participants presented data regarding the present status of the U.S. commitment in high LET radiation therapy equipment with emphasis on the physical parameters of the fast neutron-producing cyclotrons in clinical use at Texas A & M (in conjunction with the M.D. Anderson Hospital), Naval Research Laboratory and at the University of Washington in Seattle. It was agreed that further and more detailed neutron dosimetry intercomparisons between the Japanese and the U.S. fast neutron clinical facilities are necessary as a physical baseline for comparison of clinical results from the two countries.
The Japanese and U.S. scientists presented their work in basic neutron radiobiology. Before clinical results from the two Japanese neutron generators can be compared with those from the U.S. facilities, it will be necessary to conduct biological intercomparisons of the various beams in both countries. Such radiobiological dosimetry has been performed on the three neutron beams in clinical use in the U.S. and will soon be conducted on a fourth beam (Fermi National Accelerator Laboratory) which should be in clinical use within one year. Need for the intercomparison is based on the fact that the neutron spectrum, hence the biological activity, is different for each machine. The techniques for such comparisons are well established. The simplest and most direct way of accomplishing this goal is to send representatives from two or three of the U.S. groups, who have performed these measurements on the U.S. beams, to Japan to repeat the measurements on the Japanese neutron beams.
Both the U.S. and the Japanese neutron therapy groups are working on clinical trial protocols. Some of the U.S. protocols will be ready by late 1975. The Japanese protocols are presently at a somewhat earlier stage of development but are progressing rapidly. It is hoped that mutually acceptable protocols can be derived so that the results can be pooled or at least intercompared. It is proposed to begin with an exchange of working drafts of protocols now under development. This area will be the subject of much future discussion.
Radiation therapy with neutrons from Californium sources was also considered. The dosimetry problems are more difficult than with fast neutrons. Furthermore, the number of patients suitable for clinical studies with ²⁵² Cf. is limited. Thus, while there has been considerable progress in equipment development, only a few patients have been treated with such neutrons in either Japan, the U.S., or any other country.
Future programs are being planned to promote the exchange of biologists, physicists, and radiologists to interrelate research and application to facilitate the physical and radiobiological dosimetry intercomparisons between the U.S. and Japanese fast neutron generators and to unify the clinical aspects of the neutron radiation therapy program. The initial emphasis is on dosimetry intercomparisons through the use of personnel previously trained. However, in order to maintain the reliability of intercomparisons over a long interval of time and to facilitate correlation of clinical observation, additional scientists are to be exchanged for training.
Plans are being made to exchange several scientists from each side to observe and work in several laboratories in 1976. A physicist of NIRS is to be sent to M.D. Anderson/TAMVEC facility to study neutron radiation dosimetry in early 1976. Dosimetry intercomparison studies will be conducted on the cyclotron-produced neutron beams of the TAMVEC, NRL and University of Washington. A U.S. radiobiologist is to be sent to work in Japan in the spring of 1976 to investigate the biological effects of the Japanese cyclotron-produced neutrons on cultured mammalian cells and compare these results with those obtained at the Naval Research Laboratory cyclotron in Washington, D.C. Those two scientists will initiate the promotion of the
exchange of personnel.
Three senior U.S. physicists will visit Japan in April 1976 to make dosimetry measurements on the Japanese neutron generators, similar to those previously made on the U.S. generators and thus to provide data for the physical dosimetry intercomparison. Several senior U.S. radiobiologists will visit Japan in the fall of 1976 to perform the radiobiological intercomparison studies similar to those made on the U.S. neutron generators. After April 1976, a Japanese radiation physicist of IMS is planning to work with physicists in the U.S. for the purpose of observing and learning dosimetry methods, as well as collimation procedures. A radiation therapist from the NIRS experienced in radiation biology is also planning to observe and study the radiation therapy methods in use and also to observe the results in U.S.A. He will observe patients under treatment, including the acute reactions, responses to treatment and the period of recovery from the initial reactions.
The second meeting is being planned for the summer of 1976 in California to review current activities and to plan for future collaboration and exchange of information. Plans are being made to initiate cooperative investigations on biological effects of neutrons and other high LET particles. Two new cyclotrons were installed in Japan since the July meeting. It is anticipated that clinical trials on radiation therapy will begin during the fall of 1976.
The great need for the exchange of clinical protocols and the careful selection of cases for treatment are emphasized. There is a great deal of discussion on the economic feasibility and the proximity of location of the expensive equipment and facilities to patients for clinical trials. In view of the considerable expense involved in the installation of new equipment and transportation of patients, large sums will be required for supporting programs in high LET radiation therapy.