The response of experimental animal tumors to neutron radiation therapy

Abstract

Several transplantable rodent neoplasms have been treated with photons and 142-15 MeV D-T or cyclotron produced neutrons, using single doses as well as a variety of fractionation schemes and total treatment times which approach the time-dose relationships utilized in radiotherapy of human tumors. Several endpoints of response have been studied, including tumor growth delay, local tumor control and clonogenic cell survival. Responses of normal tissue, particularly skin and lung, have been used to calculate therapeutic gain factors (TGF = neutron RBE tumor/neutron RBE normal tissue). The initial single fraction studies emphasized determinations of RBE and OER and corroborated the existence of an hypoxic fraction of cells in most solid tumors which limited the effectiveness of photon treatment. TGF's were found to be considerably larger than 1.0, due to neutron RBE's as high as 3.8 for tumor damage, based principally on existence of these hypoxic cells. Extensive fractionation scheme studies have been done with a few tumor lines, including C3H mouse mammary carcinomas and R-1 rhabdomyosarcomas. The importance of hypoxia, reoxygenation, and tumor cell repopulation changes have been most thoroughly studied. However, neutron KBE's for different endpoints in the same tumor system as well as RBE and TGF for various fractionation schemes vary in a manner not easily predicted. This variability is due mostly to fluctuation in response to photons; tumor damage by neutrons varies much less as a function of fractionation scheme. This complexity of tumor response to radiation has made it difficult to select criteria which would indicate which tumors are good candidates for neutron therapy. The studies of reoxygenation in C3H mammary tumors have done much to clarify the basis of low TGF for many fractionated neutron regimes used with those tumors. Other aspects of tumor radiobiology and dose limitation by different normal tissues need to be examined using fractionated radiation.