Radiobiological philosophy of current U.S. neutron trials

The historical rationale for the start of neutron radiotherapy is critically reviewed. Although it is proven that the extent of hypoxia varies among even apparently similar tumors in man the importance of this effect on the outcome of conventional radiotherapy is unknown. Other effects controlling response are inherent radiosensitivity and cell cycle redistribution. For the first the response of tumour cells to 2 Gy of X-rays is claimed to be a reasonable predictor indicating the width of the dose effect shoulder and hence the repair capacity of the tissue. An important argument for optimizing fractionation is the difference between early and late responding tissues in the isoeffect curves for X-rays as a function of dose per fraction. According to this multiple small doses of X-rays should provide a therapeutic advantage. On the other hand there may be rapid acceleration of tumour clonogen repopulation during treatment causing a loss of therapeutic differential in case of too long protraction of treatment. No or very little fractionation effects accrue to neutrons which can therefore be administered in more comfortable schedules than X-rays. In view of these biological considerations the current U.S. neutron protocols involve rapid treatment using relatively large dose fractions. Finally the point is stressed that future emphasis must be on the development of techniques to forecast the radiation response of tumours and to select patients who benefit from neutron radiotherapy.