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A fast neutron therapy facility has been established utilizing the classical solid-pole cyclotron of the National Accelerator Centre (CSIR) in Pretoria. The neutron field is generated from the 9Be(d,n)10B reaction using 16 MeV deuterons on a thick target, yielding 0.51 cGy.min-1.microA-1 at an SSD of 135 cm. Essentially the beam characteristics concur with those measured at other centres with comparable energies.
The ENEA fast neutron dosemeter is based on a planar PADC (poly allyl diglycol carbonate) placed in a polyethylene holder. The CR-39 (registered trademark of PPG Industries Inc.) material, produced by Intercast Europe S.p.A., has been used in the routine of the Individual Monitoring Service (IMS) since 1998. Since then, acceptance tests on average sheet background track density and sheet neutron sensitivity have been made on new batches as a quality control within a quality assurance programme of the IMS of ENEA-Institute for Radiation Protection (IRP). Dosemeters were irradiated with a 241Am-Be source at ENEA-IRP and processed through a chemical etching procedure (pre-etching with 40% KOH water solution 6.25 N and 60% ethyl alcohol at 70 degrees C followed by 12 h of etching in 6.25 N KOH water solution). In this paper we present the analysis of acceptance testing data for more than 30 sheets of CR-39 plastic produced in 1998, 1999 and 2000. Moreover, we compare the performance of sheets of CR-39 of standard composition with that of sheets of CR-39 with the addition of DOP (dioctylphthalate), in different concentrations, on the hasis of average background density, neutron sensitivity and background fluctuation that limit the lower detectable dose. This study demonstrates the need for acceptance tests to assure the quality of the dosimetric performance of these dosemeters, which is considerably dependent on the quality of the CR-39 plastic.
Ehrlich's carcinoma growth inhibition was studied under the conditions of fractionated irradiation with fast neutrons and x-rays. Fast neutrons were obtained from a reaction of 13.6 MeV alpha----Be on the Y-120 cyclotron. Neutron beam irradiation doses were within 2-17 Gy, x-ray doses from 7.5 to 72 Gy. Tumors were subjected to local irradiation with 1-8 fractions at a 3-4 day interval. The results showed that an increase in the total duration of a course of irradiation and a decrease in a dose per fraction resulted in a reduced effect of carcinoma growth inhibition. At the same time, an increase in the fast neutron RBE under these conditions from 3.4 (in single irradiation) to 5.4 (in 8-fold irradiation) indicated more pronounced inhibition of reparation and/or repopulation in a tumor in neutron beam irradiation.
The effects of fast neutrons (10-100 Gy) on chromatin extracted from normal (liver of Wistar rats) and tumor (Walker carcinosarcoma maintained on Wistar rats) tissues were compared. The spectroscopic assays used were (i) chromatin intrinsic fluorescence, (ii) time-resolved fluorescence of chromatin - proflavine complexes, and (iii) fluorescence resonance energy transfer (FRET) between dansyl chloride and acridine orange coupled to chromatin. For both normal and tumor chromatin, the intensity of intrinsic fluorescence specific for acidic and basic proteins decreased with increasing dose. The relative contributions of the excited-state lifetime of proflavine bound to chromatin were reduced upon fast-neutron irradiation, indicating a decrease in the proportion of chromatin DNA available for ligand binding. The Forster energy transfer efficiencies were also modified by irradiation. These effects were larger for chromatin from tumor tissue. In the range 0-100 Gy, fast neutrons induced alterations in DNA and acidic and basic proteins, as well as in global chromatin structure. The radiosensitivity of chromatin extracted from tumor tissue seems to be higher than that of chromatin extracted from normal tissue, probably because of its higher euchromatin (loose)--heterochromatin (compact) ratio.
The WIMSD4 code was used to calculate the fast neutron flux spectrum and the fast neutron fission cross-sections for (238)U, using six energy groups ranging from 0.5 to 10 MeV. These results, with the measured radioactivities of the (140)Ba, (131)I, (103)Ru, (95)Zr and (97)Zr fission products emerging from the fission of the (238)U foil covered with a cadmium filter, were used to measure the fast neutron flux in the Syrian Miniature Neutron Source Reactor inner irradiation site.
OBJECTIVE: To evaluate the efficacy of fast neutron radiotherapy for the treatment of salivary gland neoplasms. DESIGN: Retrospective analysis. SETTING: University of Washington Cancer Center, Neutron Facility, Seattle. PATIENTS: The medical records of 279 patients treated with curative intent using fast neutron radiotherapy at the University of Washington Cancer Center were reviewed. Of the 279 patients, 263 had evidence of gross residual disease at the time of treatment (16 had no evidence of gross residual disease), 141 had tumors of a major salivary gland, and 138 had tumors of minor salivary glands. The median follow-up period was 36 months (range, 1-142 months). MAIN OUTCOME MEASURES: Local-regional control, cause-specific survival, and freedom from metastasis. RESULTS: The 6-year actuarial cause-specific survival rate was 67%. Multivariate analysis revealed that low group stage (I-II) disease, minor salivary sites, lack of skull base invasion, and primary disease were associated with a statistically significant improvement in cause-specific survival. The 6-year actuarial local-regional control rate was 59%. Multivariate analysis revealed size 4 cm or smaller, lack of base of skull invasion, prior surgical resection, and no previous radiotherapy to have a statistically significant improved local-regional control. Sixteen patients without evidence of gross residual disease had a 100% 6-year actuarial local-regional control. The 6-year actuarial freedom from metastasis rate was 64%. Factors associated with decreased development of systemic metastases included negative lymph nodes at the time of treatment and lack of base of skull involvement. The 6-year actuarial rate of development of grade 3 or 4 long-term toxicity (using the Radiation Therapy Oncology Group and European Organization for Research on the Treatment of Cancer criteria) was 10%. No patient experienced grade 5 toxic effects. CONCLUSIONS: Neuron radiotherapy is an effective treatment for patients with salivary gland neoplasms who have gross residual disease and achieves excellent local-regional control in patients without evidence of gross disease.
The involvement of the p53 gene in apoptosis of many cell types towards y-radiation is well established. However, little information is available on the relationship between p53 status and cells' ability to undergo apoptosis following exposure to fast neutrons. The aim of this study was to characterize the apoptotic pathway traveled by neutrons in mouse intestinal crypt cells. Each mouse received whole body doses of 0.25-8 Gy fast neutrons and were sacrificed 0, 4, 6, 12, 24, 48, and 72 h, respectively, after irradiation. Apoptosis of crypt cells and expression of p53, cyclin A, cyclin B, cyclin D, and cyclin E were measured. The apoptosis in crypt cells was maximal at 4 and 6 h after irradiation, showing a gradual decline at 24 h. The highest frequency of apoptosis was seen at a 1 Gy dose and then declined gradually beyond a 2 Gy dose with high levels of damage. In immunoblot analysis, apoptosis was confirmed to be dependent on p53 function after fast-neutron irradiation. In addition, cyclin B1, cyclin D, and cyclin E were overexpressed in intestinal cells after fast-neutron irradiation and their immunoreactivities were increased strongly in round and oval cells of laminar propria in villi core and crypts. The results of the current study suggest that apoptosis in crypt cells shows a time- and dose-dependent increase after fast-neutron irradiation. In addition, fast-neutron-induced apoptosis in mouse intestinal crypt cells appears to be related to the increase in functional p53 proteins to a level sufficient to initiate apoptosis and up-regulation of cell-cycle-regulated proteins, which may lead to resistance to DNA damage through cell cycle arrest, is involved deeply in protection of gastrointestinal cells after low doses of fast-neutron irradiation.
Reports indicate that cancer of the prostate, soft tissue sarcomas, salivary gland tumors, and melanomas respond well to fast-neutron treatment. To better understand the action of fast neutrons on such tumor tissues, we have begun studies with the versatile Dunning rat prostate tumor system. In our initial studies with the R3327-AT1 subline we observed a relative biological effectiveness (RBE) of approximately 3 for single doses of 14-meV fast neutrons. As a continuation of those studies the present report discusses our findings following fractionated treatments with 10 equal fractions of 14-MeV fast neutrons or 60Co gamma rays at several dose levels per fraction. After either fractionated neutron or photon treatment the volume of the tumors continued to increase for 2 weeks and then reached a plateau, the level of which was dose dependent. Tumor growth resumed and no local control was observed. Analysis of the data using growth delay as biological end point yielded an RBE of approximately 4.2 +/- 1.3.
Fast neutron therapy for locally advanced or radioresistant malignant tumors was started in November 1975 at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. To evaluate the effectiveness of fast neutron therapy, mixed neutron-photon fractionated irradiation, on squamous cell carcinoma of the uterine cervix, 98 patients with Stage IIIb disease were examined to study the correlation between local control rate and histological types. The local control rate after neutron-mixed beam therapy was 73%, which decreased to 66% with photon irradiation. The five year survival rate was 49% for patients receiving neutron therapy and 49% for those receiving photon therapy. There was no statistical significance between neutron and photon therapy; we then attempted to analyze histological types to check for any gain using neutron therapy. This study was a nonrandomized trial. The preliminary results however, gave us useful information for the next of neutron therapy.
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.
PURPOSE: The aim of this study is to report the incidence of soft tissue sarcoma in a large group of patients treated with fast neutrons. METHODS: A systematic review was conducted of long-term follow-up after trials of fast neutron therapy for cancers at various sites. The study took place at Edinburgh Cancer Centre, Western General Hospital, Edinburgh, Scotland, United Kingdom. From 1977 to 1984, 620 patients were treated using fast neutrons in the MRC cyclotron unit in Edinburgh. Most of these were treated within randomized controlled trials. Follow-up was maintained in all except 2 patients, who left the area to return abroad. The main outcome measure was the incidence of new soft-tissue sarcomas during long-term follow-up. RESULTS: Three cases of sarcoma, developing within the treatment volume, were observed in a small group of patients treated some years earlier using fast neutrons. This incidence was 111 times what would have been expected in the normal population and 15 times the incidence in a comparable photon-treated group of patients. CONCLUSION: The long-term incidence of sarcomas in patients previously treated with fast neutrons is significant.
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.
The thermal neutron flux in a fast neutron therapy treatment unit is measured by a small ionization chamber coated inside with boron (10B). These measurements are compared with calculations of the thermal neutron flux made by a pencil beam algorithm, which can be used as a first approximation for treatment therapy planning. The additional dose for boron neutron capture therapy (BNCT) as a boost in a 14 MeV neutron generator is calculated from the measured thermal neutron flux.
The effects of fractionated doses of fast neutrons (42 MeVd----Be) on the radiation response of the pig kidney have been assessed and compared with those observed after X irradiation. Following X irradiation there was a marked increase in the total dose at which renal function was preserved with decreasing fraction size. The rate of this increase was dependent on the overall treatment time; for fractionated irradiation given over 18 or 39 days the exponents related to fraction number, N, were 0.36 +/- 0.03 and 0.48 +/- 0.003, respectively. In contrast, there was no significant change in the iso-effect dose for renal injury following fractionated irradiation with fast neutrons where there was also little effect of varying the overall treatment time. Analysing these data by means of the linear-quadratic (LQ) model, using both an Fe-plot and the Tucker test, gave alpha/beta ratios of 2.42 +/- 0.06 Gy and 2.99 +/- 0.16 Gy, respectively, for X-ray doses given in 18 days. For fractionated doses of X rays given in 39 days the alpha/beta ratios were 0.40 +/- 0.01 Gy and 0.47 +/- 0.02 Gy, respectively. The alpha/beta ratios for renal tissue following fast neutron irradiation obtained by the two methods were also similar, i.e. 15.00 +/- 0.60 Gy and 15.72 +/- 3.76 Gy, respectively. The pronounced fractionation effect seen with X irradiation, particularly for doses administered over 39 days as opposed to 18 days, coupled with the absence of any such effect with fast neutrons, resulted in a marked increase in relative biological effectiveness (RBE) with decreasing X-ray dose/fraction. The slopes of the resulting regression lines were -0.73 +/- 0.05 and -0.33 +/- 0.02, respectively. The lack of dose sparing associated with fractionation, or variation of the overall treatment time for fast neutron irradiation, suggests that doses administered to tumours adjacent to the kidney can be given as a few relatively large dose/fractions in a short overall treatment time without an increased risk of complications related to renal tissue. This may be of therapeutic advantage in the treatment of rapidly proliferating tumours where dose may be wasted using more conventional protracted fractionated irradiation schedules.
The results of combined radiotherapy with fast neutrons and photons for 39 malignant gliomas were analyzed. The patients consisted of 16 astrocytoma grade 3 and 23 glioblastoma multiforme. There were two kinds of combination methods which were either "boost therapy" or "mixed beam therapy" with a localized fast neutron field. The average dose of fast neutrons was 569 cGy (n, gamma) and that of photons was 36.86 Gy. The median survival of astrocytoma grade 3 was 15.5 months, and that of glioblastoma multiforme was also 15.5 months. With respect to the combination methods, there was no difference between the boost regimen and the mixed beam regimen. This result seems to have no impact on survival compared to other reports. Patients' ages, surgical debulking procedures, and photon doses were listed as significant prognostic factors, but doses of fast neutrons had no prognostic significance for survival. Because there were no moderate or severe complications for the brain except permanent epilation in all cases, neutron dose escalation study with a localized field will be recommended.
Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness (RBE) of fast neutrons on normal pulmonary tissue. The right anterior abdomen was included in the field of radiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250 or 3375 rad in four fractions per week for six weeks. Fifteen dogs received 3000, 4500 or 6750 rad of photons (five/group) in an identical fractionation pattern. All neutron irradiated dogs receiving 3375 and 2250 rad and one receiving 1500 rad developed clinical signs of pancreatic, hepatic and gastrointestinal disturbances. The liver enzymes of these dogs became elevated and they died or were euthanatized in extremis 47-367 days after irradiation. Only one 6750 rad photon dog developed similar signs and died 708 days post-irradiation. Five neutron and 10 photon exposed dogs died of other causes. Neutron-induced lesions in the stomach and duodenum included hemorrhages, erosions, ulcerations and fibrosis. Ulcers perforated the GI tract of five dogs. Pancreatic lesions included degranulation and necrosis of acinar cells, fibrosis ans atrophy. Islet cells were not obviously damaged. All lesions were associated with degenerative and occlusive vascular changes. The RBE of fast neutrons, assessed by clinical signs, gross and microscopic pathology, is approximately 3-4.5 for pancreas and about 4.5 for pylorus and duodenum.
PURPOSE: We analyzed the characteristics of radiosensitivity and potentially lethal damage repair in the quiescent cell populations of murine SCC VII solid tumors irradiated with fast neutrons, in comparison with those irradiated with 10 MV X rays. METHODS AND MATERIALS: SCC VII tumor-bearing C3H/He mice were irradiated with 30 MeV fast neutrons or 10 MV X rays after receiving 10 injections of 5-bromo-2'-deoxyuridine (BUdR) to label all proliferating tumor cells. Immediately or 24 h after irradiation, the tumors were excised and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus frequency in cells without BUdR labeling was determined using immunofluorescence staining to BUdR. This micronucleus frequency was then used to calculate the surviving fraction of unlabeled cells from the regression line for the relation between micronucleus frequency and the surviving fraction of all tumor cells. Thus, a cell survival curve could be determined for the cells not labeled by BUdR, which can be regarded as the quiescent cells for all practical purposes. RESULTS: The difference in intrinsic radiosensitivity between all tumor and quiescent cells became smaller by using fast neutrons, compared with X rays, especially when large radiation doses were given. Potentially lethal damage repair by quiescent cells was less evident following irradiation with fast neutrons than with X rays, especially when large doses were delivered. CONCLUSION: By using fast neutrons in clinical radiotherapy, the radiosensitivity of solid tumors is thought to depend on their heterogeneity less critically than for X rays.
252Cf is a neutron emitting radioisotope which has promise for both standard brachytherapy and neutron capture enhanced brachytherapy. In this study, experimental measurements and calculations were used to determine the thermal neutron fluence rate, phi(th) [n cm(-2) s(-1) mg(-1)], in the vicinity of 252Cf applicator tube (AT) type sources. Results of these measurements were confirmed with Monte Carlo calculations performed in a distributed manner on multiple workstations using MCNP. Three studies were executed: (1) relative phi(th) as a function of distance from a 252Cf AT source in an A-150 tissue equivalent plastic phantom using thermoluminescent dosimeters (TLDs) of varying 6Li/Li enrichment, (2) phi(th) measured with gold foils in a 114 liter water phantom 5 cm from two 252Cf AT sources, and (3) calculations of the impact of phantom material composition (e.g., A-150, water, brain, muscle) on phi(th) from moderated 252Cf fast neutrons. TLD results and Monte Carlo calculations in A-150 of relative phi(th) typically agreed within 1% and at most differed by 3% for distances from 1 to 6 cm. Foil measurements followed the ASTM E 262-86e protocol, and the ratio of activated plain and Cd encased gold foils (7.31) agreed well with the calculated ratio (7.26). Measured phi(th) at 5 cm (1.70+/-0.10 x 10(7) n cm(-2) s(-1) mg(-1)) was 10% greater than that determined using MCNP (1.55+/-0.12 x 10(7) n cm(-2) s(-1) mg(-1)), but was within the combined uncertainties. Compared with A-150 at a distance of 1 cm, phi(th) was 20%, 22%, and 32% less for water, brain, and muscle, respectively; these ratios decreased to 16%, 16%, and 24% less, respectively, at a distance of 5 cm from the source in a 15 cm diameter phantom. Comparisons of these results generally agreed with those in the literature for a value of 2 x 10(7) n cm(-2) s(-1) mg(-1) in water at 3 cm.