On the repair of sub-lethal damage in V79 Chinease hamster cells resulting from irradiation with fast neutrons or fast neutrons combined with X-rays.
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Animals↗
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Study on the biological effect of fast neutrons 1. Effect of fast neutrons on germinability of barley seeds and on the chlorophyll content of the seedlings according to the dose used.
Barley seeds were irradiated in the active zone of the reactor at 500 watt, at favourable flux of fast neutrons in the dose interval of 823--2144 rad. Seeds after irradiation were "cooled" for 48 hours, then germinated, and the length of shoots of the seven days old seedings was measured. The value of the half lethal dose is 1130 rad, estimated from the growth curve. There is a well-defined relation of chlorophyll content (calculated for fresh weight unit) to the dose used. It was concluded from the phenotype of the leaves that the decrease of chlorophyll content was due first of all to the presence of chlorophyll-less cells and cell lines and not to the decrease of chlorophyll content of the individual cells. Irradiation yielded genetically defected cells.
Chlorophyll↗
An historical survey of radiobiology and radiotherapy with fast neutrons.
The treatment of cancer using fast neutrons was first attempted from 1938 to 1942, only a few years after the identification of the particle in 1932. The radiobiological information which was available at that time was both inadequate and contradictory, and provided no definite rationale for using neutrons in preference to X-rays. The doses given were often too high, causing many patients to suffer severe late reactions. As a result, further attempts to use fast neutrons in radiotherapy were abandoned for nearly 30 years. Interest in the use of fast neutrons was stimulated again by the elucidation of the oxygen effect and the discovery that it was less for neutrons than for X-rays. Thus tumours containing hypoxic cells would be less protected against neutrons. Also the reduced repair of sublethal damage with neutrons provided at least a partial explanation of the miscalculation of dose in the early trial. This was confirmed by means of a series of experiments on pig skin, from which it was also concluded that late damage was not more severe after neutrons, compared with X-rays for a given degree of early damage. A new clinical trial began in 1966, and the results so far are encouraging. In order to relate radiotherapy experience with X-rays to neutrons, it is necessary to measure the relative biological effectiveness (RBE) of neutrons. This has been done for skin of man, pig, mouse and rat. Because of the smaller recovery from sublethal damage after neutrons, the RBE increases as the dose per fraction decreases, but the relationship between RBE and dose per fraction is the same for all four species. Similar information, but only for rodents, has been obtained for a variety of other normal tissues with both cyclotron-produced and monoenergetic 14 or 15 meV neutrons. Experiments with animal tumours have indicated that there might be a wide variation in RBE from tumour to tumour due both to the presence of hypoxic cells and to differences in their capacities to recover from sublethal damage after X-rays and neutrons. The largest series of experiments on one tumour shows that whereas certain fractionation techniques with X-rays may produce a poor tumour response for a given level of normal tissue damage, all the neutron regimes produced a similar, close to optimum result. There is no evidence from which to expect any special dangers from neutron irradiation, and their likely advantage is that they may provide a more reliable method of radiotherapy as well as sterilizing some tumours which are normally resistant to X-rays.
Animals↗
[Neutron therapy in the G.D.R. Fundamentals of fast neutron application in radiation treatment (author's transl)].
In 1972 GDR started with the treatment of tumor patients with fast neutrons on the base of oxygen-effect. That means a better sensitivity of radiation of anoxic cells against radiation with high LET in comparison to radiation of thin ionization. Every tumor contains some anoxic cells. Therefore a better effect is possible with doses that are tolerated by normal tissue. In the following the details of the problems are discussed.
Anaerobiosis↗
Transfer dosemeters for fast neutron sources.
The increasing use of fast neutron sources in radiobiology, radiotherapy, etc. makes dosimetry intercomparisons (intercalibrations) by mail desirable. After comparing the relative advantages and disadvantages of the various available integrating fast neutron detectors, fission fragment track etching was chosen because such detectors can be made sufficiently small, rugged, fading resistant, inexpensive and accurate. Using several combinations of 232Th or 237Np as fissile materials, and organic and inorganic track detectors, it was established that both automatic spark counting and visual track counting techniques can be developed to cover the desirable dose range (approximately 50-500 rad) with sufficient accuracy (sigma less than or equal to 5%). One possible source of errors is the overlapping size distributions of fission fragment and recoil particle tracks in organic foils exposed at high neutron energies. Several approaches to reduce this problem are discussed.
Fast Neutrons↗
A new polycarbonate fast neutron personnel dosimeter.
Registration of fast-neutron-induced recoil and (n,alpha) tracks directly in sensitive polymers especially polycarbonate foils when etched by the electrochemical etching (ECE) method provides a simple, sensitive, and inexpensive means of fast neutron dosimetry. The wide dose range and a dose equivalent response, negligible fading rate, and insensitivity to X, beta, and gamma radiations make such a method feasible for many neutron dosimetry applications, especially personnel dosimetry. Due to very large size of the tracks, even the unaided eye can be used as a reading device.
Carbonates↗
Accelerated fast neutron therapy: a pilot study.
The clinical role of fast neutron therapy has been limited by excessive late normal tissue damage. A pilot study of accelerated fractionation of fast neutron therapy was performed, based on the rationale that this should result in an increase in the response in acute reacting tissues (normal and malignant), with no change in late damage and a consequent increase in the therapeutic ratio. Further accelerated fractionation should improve the local control of rapidly proliferating tumour, without the potential problem of inadequate reoxygenation inherent in accelerated photon schedules. 6 or 12 fractions of 62 MeV (p-Be) neutrons were given over 12 days to 27 sites in 23 patients with locally advanced tumours. With a dose reduction of 12% (18 Gy), acceptable skin and oral mucosa early reactions were obtained. A larger dose reduction (15%) was required at pelvic sites. The incidence of late EORTC/RTOG grade 4 toxicity was 46%. The overall response rate was 76% with a complete response rate of 16%. For locally advanced breast cancer, the complete response rate was 9%, which compares unfavourably with previous results with conventional neutron fractionation schedules. The combination of a low overall complete response rate and excessive late normal tissue toxicity suggests that accelerated fractionation of fast neutrons does not lead to an improvement in the therapeutic ratio, and that late normal tissue damage will continue to be dose limiting.
Adult↗
Fractionated dose of 35-MEV fast neutrons and hypoxic tumor cell survival curve.
The determination of the RBE for the MANTA fast neutrons produced by NRL is inprogress, with the model system using tumor cell population kinetic response patterns assayed in vitro after irradiation in vivo. Ascites tumor cells BW-5147 were irradiated with a clinically usable fast neutron beam from the NRL cyclotron, which is produced by accelrating deuterons to 35 MeV and using htem to bombard a thick berylliumtarget. The comparison of dose-effect relationships was made for doses ranging from30 to 1000 rads. The doses required for an isoeffect on BW-5147 hypoxic tumor cell survival and impairment of its reproductive capacity from fast neutron exposure were not different wheither it was given a single dose or the same dose given in three fractions separated by long recovery periods in situ. No intracellular repair of sublethal injury when the dose was given in three fractions, although the hypoxic BWp5147 tumor cells haveno effective reoxygenation or repopulation in this time interval. The RBE for the fast neutron beam is 4 relative to x rays for fractionated doses at the surviving fractionlevel of 0.6-0.7, while the RBE IS 2.5 FOR SINGLE DOSES. However, at a surviving fraction of 0.1, the RBE is 1.9 for single and 2.8 for fractionated doses. Analysis of thedaily cell population rate or mitotic delay between the two types of radiations at a similiar level of survival.
Animals↗
A thermoluminescent fast-neutron dosemeter based on pellets of CaSO4: Dy mixed with sulphur.
The fast neutron activation reaction 32S(n, p) 32P in CaSO4: Dy has been used in the measurements of fast neutron dose by employing a post-irradiation TL accumulation method. In order to increase the efficiency of the method CaSO4: Dy powder was mixed with sulphur powder in various proportions from which pellets weighing each were made. After neutron irradiation these pellets were each burnt in an aluminium planchette and the phosphor residue with 32P beta activity on it was allowed to undergo self-irradiation for TL accumulation. The fast neutron efficiency of the system employing 10 pellets of 0.1% CaSO4: Dy was found to be about 100 times that of bare CaSO4: Dy powder.
Calcium↗
Fast neutrons from a 25-MeV betatron.
Since published results for the fast-neutron dose per x-ray rad from high-energy therapy installations have differed by as much as a factor of 300, we have measured the neutron production from our 25-MeV betatron. Fast-neutron activation of aluminum foils was the method used. The effect of photoneutron production in the detectors, which has affected some past work, has been eliminated. A major source of neutrons in the treatment field was the platinum target. The neutron spectra used in the calculations of fluence were obtained by interpolation between published energies and between neighboring elements. Fluences per rad of x rays without a phantom were largely independent of field size and energy in the range 18-23 MeV. At 100 cm SSD and 23 MeV a large beam flattener contributed 15% of the neutrons, the remainder coming equally from the target and background. A phantom increased the neutron fluence/rad of x rays by 0%-10% depending on the field size. At 23 MeV we estimated the neutron dose to a patient to be 2.2 X 10(-4) rad per rad of x rays inside the treatment field and 3 X 10(-5) at 20 cm outside the field. The uncertainty in these figures is believed to be +/- 50%. In the electron beam the neutron dose per rad was about 50 times smaller than in the x-ray beam. Estimates were made of neutron fluences at other energies and target thicknesses. We discuss our results in comparison with those of others.
Fast Neutrons↗
Radioresistance of mongolian gerbils. Fast neutrons.
Seventy-six 8 week old Mongolian gerbils were exposed to acute, whole-body fast neutrons produced by The University of Michigan 83-in. cyclotron. Groups of seven or eigth gerbils were given doses between 485 and 881 rad at 25 rad per minute. The LD 50/30 determined by probit analysis was 750 rad, with 95 per cent fiducial limits of 733 and 776. For the 50 per cent mortality level, an r.b.e. of fast neutrons compared with cobalt-60 of 1-45 was determined. For the same end-point, the r.b.e. for fast neutrons compared with X-rays is 1-33. Mortality data, body-weight and microhaematocrit changes are discussed.
Animals↗
The use of 10B to enhance the tumour dose in fast-neutron therapy.
Incorporation of 10B in tumours treated by fast-neutron therapy would increase the tumour dose via the reaction 10B(n, alpha)7Li which occurs with partially thermalised neutrons. The extent of the dose enhancement was measured for neutron beams with median energies of 2.4, 3.3, 7.0 and 9.0 MeV by two techniques: with a BF3 proportional counter in three beams and activation of 23Na in the fourth. The results obtained with the two techniques are in good agreement. The magnitude of the dose enhancement depends upon the depth, field size and neutron beam energy. The dose enhancement at a depth of 8 cm varied from 0.32% with the lowest-energy beam to 0.07% with the highest-energy beam for each microgram of 10B uptake per gram of tissue. The products of the reaction in 10B would, however, have an RBE about twice that of the fast-neutron dose in the absence of boron. The method may be useful if drugs providing adequate uptake of 10B can be synthesised.
Beryllium↗
Preliminary report of the M. D. Anderson Hospital/Texas A & M variable energy cyclotron fast-neutron therapy pilot study.
The records of 248 patients treated with fast neutrons and of 102 comparable but nonrandomized control patients treated conventionally with photons, surgery, or combined surgery and photon irradiation were reviewed. Fast neutron therapy included treatment with neutrons alone, a neutron boost after photon therapy, or a schedule of alternating neutron and photon treatments (mixed beam). The results with mixed beam irradiation were superior to those obtained with the other neutron therapy techniques, and compared favorably with the results of standard treatment methods. However, the lack of a conclusive advantage for neutron therapy in this pilot study illustrates the need for on-going randomized clinical trials.
Adenocarcinoma↗
Adenocarcinoma of the stomach: radiological and pathological correlation of effects of treatment with fast neutrons.
During the past six years 40 patients have been treated with fast neutrons for inoperable adenocarcinoma of the stomach. A number of these patients have been studied in detail both radiologically and pathologically with regard to the effects of fast neutrons on both the tumour and normal stomach. After treatment there was a constant reduction in size of the stomach capacity when compared with a control group and the motility of the stomach was lost. Mucosal changes, which were noted radiologically, appeared to be dose related. Histologically most of the tumour was destroyed. Small clumps of cells were, however, found in all except one of the patients but only in areas of the stomach which had not received the standard dose. Marked fibrosis occurred and it is our impression that the amount of fibrosis is in excess of that seen with other forms of radiotherapy.
Adenocarcinoma↗
Fast-neutron radiobiology and radiotherapy.
The application of fast neutrons, negative pions or heavy ions will only provide an advantage for the radiotherapy of cancer if, in comparison with conventional radiations, e.g., X-rays, gamma rays and electrons, better depth-dose and collimation characteristics or specific radiobiological dose response relationships result in greater local control probabilities for tumours without increased frequencies of severe noraml tissue damage. Differences in intrinsic radiosensitivity and the presence of hypoxic cells are considered to be the main factors which can cause values of the relative biological effectiveness (RBE) for responses of tumours to be larger than RBE values for normal tissue tolerance. Clinical studies on lung metastases irradiated with single dose of 15 MeV neutrons indicate that RBE values for tumour growth delay can vary between 1.2 and 4.0, while RBE values for damage to several normal tissues are estimated from corresponding animal data to be approximately 2.5.
Dose-Response Relationship, Radiation↗
High energy fast neutrons from the Harwell variable energy cyclotron. I. Physical characteristics.
A high energy fast neutron beam potentially suitable for radiotherapy was built at the Harwell variable energy cyclotron. The beam line is described and results are given of physical measurements on the fast neutron beams produced by 42 MeV deuterons on thick (4 mm) and thin (2 mm) beryllium targets. With 20 muA beam current the entrance dose rate in a phantom 150 cm from the target was about 130 rad min-1 with the thick target and about 60 rad min-1 with the thin target. Therefore, it is possible to use both the thin target and the relatively large target-skin distance of 150 cm to improve depth dose for radiotherapy or radiobiology. With this arrangement the dose rate decreased to 50% at depths in the phantom of 11.3-15.4 cm, depending on the field size. The use of primarily hydrogenous materials for shielding and collimation provided beam edge definition similar to that of 60Co teletherapy units, and off-axis radiation levels of approximately 1% which compare favorably with 14 MeV deuteron-tritium generators. The copper backing of the thin target became highly radioactive and an alterative material may be preferable. Biologic characteristics of the beam are described in a companion paper.
Fast Neutrons↗
Relative measurements of fast neutron contamination in 18-MV photon beams from two linear accelerators and a betatron.
Fast neutron contamination in photon beams in the 20 MV range have been reported in recent years. In order to determine if the variations were due mainly to differences in measurement procedures, or inherent in the design of the accelerators, three different 18-MV (BJR) photon beams were compared using identical analytical techniques. The units studied were a Philips SL/75-20 and a Siemens Mevatron-20 linear accelerators and a Schimadzu betatron. Gamma spectroscopy of an activated aluminum foil was the method used. By comparing the relative amounts of neutron contamination, errors associated with absolute measurements such as detector efficiency and differences in activation foils were eliminated. Fast neutron contaminations per rad of x rays in a ratio of 6.7:3.7:1 were found for the Philips, Schimadzu and Siemens accelerators, respectively.
Fast Neutrons↗
Systematic multi-modal treatment of osteosarcoma, with special reference to the role of fast neutron radiotherapy.
Sixty-one patients with osteosarcoma were treated. Twenty-four of these patients were managed with our systematic multi-modal treatment. Overall survival rate was markedly improved chiefly by intensive systemic chemotherapy with multiple drugs, especially adriamycin and high dose methotrexate. Preoperative regional intra-arterial infusion of anti-tumor drugs and fast neutron radiotherapy were employed and it was suggested that fast neutron had a higher relative biological effectiveness and a greater therapeutic gain factor as compared with X-rays. Fast neutron radiotherapy can play a significant role in the very systematic treatment of osteosarcoma and is specifically useful for preservation of the affected limbs.
Adolescent↗