A method for selective evaluation of the effectiveness of fast neutrons in radiotherapy

A methology is proposed for extracting and analyzing specific fast neutron effects on radiotherapy. This should be applied to the 1,500 patients treated at NIRS, Chiba in the past ten years. As the patients have been treated with different modalities based on generally combined radiation or neutron boost techniques at first the biologically equivalent doses per fraction for the photon and neutron component according to the Ellis concept were derived. In a second step treatment parameters, as the dose components and total dose as well as diagnostic parameters (tumor typing, grading and staging) will be related to the clinical outcome (survival, local control etc.). This may be done by multivariate discriminant or survival analysis.     

Irradiation of the microvasculature with fast neutrons.

Single- and split-dose irradiation of the eyes of dogs was performed with cyclotron-produced polyenergetic neutrons at a rate of about 0.2 Gy (20 rad) per minute. Neovascularization was subsequently induced surgically in the avascular corneas and stimulated for 7 days to study the response of slowly proliferating capillary endothelial cells. Corneal tissue samples were evaluated quantitatively by morphometric methods. A dose-response curve was drawn by plotting per cent capillary volume versus dose. D0 was 2 Gy (200 rad), and the recovery ability was determined to be equivalent to 1.3 Gy (130 rad). Depending on the level of damage, relative biological effectiveness (RBE) values were 1.9 to 2.3.     

Relative biological effectiveness of accelerated heavy ions and fast neutrons estimated from frequency of aberration mytoses in the retinal epithelium]

Analyzed was the literature and authors' experimental data concerning lesion and recovery of epithelium cells of mice retina immediately and long after irradiation at different sources including single and partly fractionated irradiation by gamma- and X-rays, accelerated protons, helium, carbon and boron ions, and fast neutrons of the reactor range in a large spectrum of doses and LET. Reviewed are some new techniques of determining the RBE coefficient for these types of radiation; large values of the RBE coefficients for accelerated ions and neutrons (5-10 times higher than RBE coefficients calculated for the next day following irradiation) are a result of integration into calculation of the available data about the delayed disorders in retinal epithelium cell regeneration.     

Clinical experience with fast neutrons in Amsterdam.

Since November 1972 a pilot study of fast neutron therapy has been carried out in Amsterdam at the Antoni van Leeuwenhoek Hospital (the Netherlands Cancer Institute). With a d + T machine almost 200 patients were treated in 2 years. In this paper the preliminary results will be discussed.     

Dose-response and relative biological effectiveness of fast neutrons: Induction of apoptosis and inhibition of neurogenesis in the hippocampus of adult mice

Purpose:?Our study compared the effects of high linear energy transfer (LET) fast neutrons on the induction of apoptosis and reduction of neurogenesis in the hippocampus of adult ICR mice with those of low-LET ⁶⁰Co γ-rays, to evaluate the relative biological effectiveness (RBE) of fast neutrons in the adult hippocampal dentate gyrus (DG).

Materials and Methods:?The mice were exposed to 35 MeV fast neutrons or ⁶⁰Co γ-rays. We evaluated acutely the incidence of apoptosis and expression of Ki-67 (a protein marker for cell proliferation originally defined by the monoclonal antibody Kiel-67) and doublecortin (DCX: an immature progenitor neuron marker) in the hippocampus after a single whole-body irradiation.

Results:?The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL)-positive apoptotic nuclei in the DG increased and both Ki-67- and DCX-positive cells declined in a dose-dependent pattern, with fast neutrons or γ-rays. In the hippocampus, which showed an apoptosis frequency between 2 and 8 per DG, the RBE of fast neutrons was approximately 1.9. Additionally, the inhibitory effects of fast neutrons on the expression frequencies of Ki-67 (4–8) and DCX (8–32) were approximately 3.2 and 2.5 times, respectively, the effects of γ-rays at the same dose.

Conclusions:?Increased apoptotic cell death and decreased neurogenesis in the hippocampal DG were seen in a dose-dependent pattern after exposure to fast neutrons and γ-rays. In addition, the different rate of hippocampal neurogenesis between different radiation qualities may be an index of RBE.     

Determination of air/water ratio in pipes by fast neutrons: Experiment and Monte Carlo simulation

Fast neutron dose attenuation from a ²⁵²Cf neutron source is used for the determination of air to water ratio in pipes. Such measurement of the two-phase flow volume fraction is important for many industrial plants such as desalination plants and oil refineries. Fast neutrons penetrate liquid more than slow neutrons or gamma rays. Using diameters from 11.5 cm to 20.76 cm and with wall thicknesses from 0.45 to 1.02 cm, attenuation was independent of pipe wall thicknesses and diameters. Experimental data was in good agreement with values calculated using MCNP codes. The measured neutron flux values decreased with increasing water levels in pipes up to about 14 cm, indicating that our system can be used successfully in desalination plants in pipes of different sizes. The experimental sensitivity was found to be about 0.015 mSv/h cm and the system can be used to measure water level changes down to few millimeters. Use of such a system in fixed positions in the plant can provide information on plant's overall performance and can detect loss of flow immediately before any consequences. A portable system could be designed to measure the air to water ratio in different locations in the plant in a relatively short time.     

The role of fast neutrons in radiooncology--a critical appraisal.

The contribution of fast neutrons to local tumour control has been investigated worldwide since the mid-60's in more than 20 institutions. The high expectations anticipated from the promising results of experimental studies could not be adequately realized in the clinic. The late normal tissue damage was unacceptable due to poor depth dose characteristics and further technical limitations of the first generation low-energy machines. Even with sophisticated therapy planning systems and high-energy cyclotrons as well as comparable late normal tissue damage as witnessed after photons, only a few tumour entities have responded superiorly to fast neutrons. These particularly include macroscopic tumours of the salivary glands, prostate and, potentially, soft and osseous tissues. The role of fast neutrons for head and neck cancer has not yet been definitely proved. For bladder-, cervical- and rectal carcinomas, non-small cell lung-, pancreatic- and breast cancers as well as malignant gliomas, no therapeutic benefit as compared with photons was observed in the case of macroscopic residual or inoperable recurrent tumours.