Fast-neutron-beam therapy and low-dose-rate fast-neutron intracavitary therapy of cervical carcinoma are effective in producing regression of advanced tumors. However, effectiveness is critically dependent on the schedule by which they are used in combination with fractionated external low-linear-energy-transfer (LET) therapy. Neutron-beam therapy is now alternated frequently with fractionated external radiotherapy (mixed beam). Intracavitary neutron therapy, scheduled before fractionated external-beam photon therapy, was maximally effective. These findings indicate that traditional concepts developed for the use of conventional low-LET therapy may need to be altered to use neutrons for therapy and to achieve improved local control of advanced cancers.

The EMT6 tumour of the Balb/c mouse and the LSA ascites lymphoma of the C57BL/YM mouse have been used to study the effects of Cf-252 neutrons at low dose rates. EMT6 and LSA cells were irradiated in vitro in a hypoxic state; EMT6/KY cells were plated after exposure for colony-forming ability assays, while TD50 assays were used to test the tumour-forming ability of LSA cells. EMT6 cells showed r.b.e.n values of 5.3, 4.7, and 3.0 for Cf-252 dose rates of 26.8, 10.2, and 5.2 cGy/hour (= rad/hour), respectively, when compared to Cs-137 irradiations at dose rates of 79.7, 25.7 and 12.1 cGy/hour, respectively. The LSA ascites gave r.b.e.n values of 5.6 and 5.2 at dose rates of 27.0 and 6.94 cGy/hour of Cf-252, when compared to Cs-137 irradiations at 79.6 and 24.9 cGy/hour, respectively. However, changes in r.b.e. values for both systems were entirely dependent on comparison with Cs-137 survival curves.

HeLa cells were implanted into athymic nude mice from tissue culture and solid tumors established (HeLa cell tumor or HCT). Large cell numbers of 1 x 107 were required to obtain consistent and progressive growth, and tumor growth followed a Gompertzian mode. Irradiation studies were carried out using acute Cobalt‐60 (60Co), low‐dose‐rate (LDR) Cs‐137 and LDR Cf‐252. Cf‐252, a neutron‐emitting radioisotope, produced an immediate tumor shrinkage and regression response after a dose of 279 cGy. Acute 60Co or LDR Cs‐137 irradiation with 1000 cGy had little effect on the HCT. After a dose of 2000 cGy of 60Co radiation tumor shrinkage followed a latent period of approximately 5 days. Cisplatin had no effect on the HCT in nude mice in stationary or late exponential growth.

Clinical data of the University of Kentucky trial using californium (252Cf), or caesium (137Cs), are reviewed for dose-response based on the endpoint of tumour eradication estimated from hysterectomy specimens obtained 4-6 weeks after preoperative irradiation. These data are used to assess the relative biological effectiveness (RBE) for 252Cf neutrons compared with 137Cs gamma radiation. Tumours treated were of common stage but were of bulky or barrel shape suitable for "radiosurgical" therapy. Dose-response curves were constructed, and additional data from the literature used to analyse the curve shape. The photon dose-response curve is complex on a logarithmic plot, whereas the 252Cf neutron curve is exponential. This indicates that the RBE can be different depending on the number of implants, schedule and size of dose delivered per session. The RBE values were approximately 8.0 at low doses or for multiple implants but they may rise to approximately 16 at larger doses or for single 252Cf implants.

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