Response of EMT-6 Tumors to Single Fractions of X Rays and Cyclotron Neutrons: Evaluation and Comparison of Multiple Endpoints

EMT-6 cells growing in vitro or as solid tumors were treated with single fractions of 250-kVp X rays or cyclotron neutrons (21.5-MeV ${\rm d}^{+}$ on Be). The neutron RBEs for cell survival in vitro are 1.5 to 1.6 in the exponential region, less than the RBEs of 1.8 to 2.5 for mitotic delay. The relatively greater delay produced by neutrons can influence cell progression and also response of survivors to subsequent doses of radiation in a manner different from that occurring after an X-ray dose isoeffective for cell killing. The in vivo endpoints of tumor response examined were clonogenic cell survival, local tumor control, and growth delay. RBEs for growth delay range from 2.3 to 2.4, but are not statistically significantly different from RBEs for cure or clonogenic cell survival. The large neutron RBE of 3.0 for clonogenic cell survival at intermediate as well as high doses is based on apparent tumor hypoxia caused by anesthesia. The low neutron RBE of 1.7 for local control is due to immunosuppression caused by leakage and scatter neutron radiation to the animal's body during localized treatment of the tumor; leakage and scatter whole-body photon exposure is negligible. Low-dose whole-body neutron irradiation reduces the TD50 in mice preimmunized with heavily irradiated tumor cells. This is consistent with the above explanation of the lowered RBE for local tumor control.