Radiobiological research with fast neutrons and the implications for radiotherapy.

Abstract

There has recently been an upsurge of interest in the use of high linear energy transfer (LET) radiations in radiotherapy (21). At the present time a beam of fast neutrons is the only type of radiation available with a LET substantially higher than that of x rays. The physical and radiobiological properties of the fast neutron beam generated by the Medical Research Council cyclotron at Hammersmith Hospital are being investigated with radiotherapeutic applications in mind, and a number of results up to the beginning of 1962 have already been published as a symposium (16). The work has now reached a stage where the treatment of patients can be considered, and the purpose of the present paper is to summarize the results to date and to relate them to the problem of radiotherapy with high LET radiation. A beam of fast neutrons of several MeV is sufficiently penetrating for therapy of deep-seated cancer. A monoenergetic beam of 14 MeV neutrons has depth-dose characteristics similar to those of megavoltage x rays (19). The neutron beam at Hammersmith is produced by directing a beam of 16 MeV deuterons onto a thick beryllium target. The spectrum extends up to 19 MeV with a modal value at about 6 MeV. The depth-dose distributions are similar to those of 250 kV x rays, making therapy possible at many sites. The LET spectrum in tissue is complex, extending from low values characteristic of gamma radiation up to nearly 1,000 keV/μ. It is not meaningful to describe the distribution in terms of a single effective LET since different parts assume varying degrees of importance depending on circumstances, e.g., test material, size of dose, presence of oxygen or chemical protectors, etc. Since the publication of the symposium in 1963 (16), the neutron target has been removed to a new position, allowing experiments to be performed in a separate room next to the cyclotron chamber (10). This change has been of great value and makes the treatment of patients possible. Basic physical information about the beam is given elsewhere (8, 10). Oxygen Ratios The rationale for using fast neutrons or other high LET radiations in radiotherapy lies in their reduced oxygen enhancement ratio. The maximum dose of radiation which can be delivered depends on the response of normal tissues which are mostly well oxygenated; the oxygen enhancement ratio indicates the reduction in effective dose received by anoxic regions in a tumour. Consequently the ratio of the two oxygen enhancement ratios, that of x rays to that of neutrons, gives the increase in the effective dose received by these regions when neutrons rather than x rays are used. This ratio has been called the Gain Factor by Alper (1). Table I gives all the results of measurements of this type, which have been made using the fast neutron beam. The bacterial experiments given at the bottom of the table were designed to assess the effects of different culture conditions during and after irradiation.