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PubMed1994

Fast neutron therapy. The UK experience.

Following conflicting results from Hammersmith and Edinburgh, the 62.5 MeV (p-->Be+) Douglas cyclotron was installed at Clatterbridge in order to carry out further studies with fast neutrons. Several features were incorporated into the study design to achieve as unbiased as possible a comparison between 62.5 MeV neutrons and conventional 8 MV x-ray therapy. Interim analysis of 151 patients in the pelvic study in the autumn of 1989 revealed a trend towards a worse survival in the neutron therapy group which soon became significant, leading to study termination in February 1990. The reasons for this diminished survival were unclear; with no significant difference in morbidity. Although the incidence of metastases was initially higher in the neutron patients than the photon patients this difference was not sufficient to explain the survival difference. Considerable morbidity would be expected from photon therapy using the same fractionation as was used in the neutron arm of the trial. If further neutron therapy at this energy is planned consideration should be given to the use of smaller fractions.

Fast Neutrons↗
PubMed1989

[Changes of the cytogenetic effectiveness of the therapeutic ray of fast neutrons in water phantoms].

Changes of cytogenetic effectiveness of the therapeutic ray of fast neutrons were studied in water phantom in the Medical-Biological Complex of CyclotronU-120 at the Institute for Nuclear Research of the Academy of Sciences of the Ukrainian SSR. Investigations were done in a culture of lymphocytes of the peripheral human blood by means of metaphase method to find out chromosomal aberrations. The neutrons were generated by firing a thick beryllium target with a 13.6 MeV-deuteron ray in the nuclear reaction 9Be (d,n) 10B. The investigated dose range was 25-220 cGy. The results of the studies demonstrate that the cytogenetic effectiveness of radiation is reduced with increasing depth of the water phantom. The maximum reduction of the effect was seen in a depth up to 6 cm, which is attached to absorption of low-energetic neutron fraction. The obtained results confirm necessity of to filter the therapeutically applicable beam of neutron radiation.

Cells, Cultured↗
PubMed1991

The lethal effects of Fermilab fast neutrons vary with the depth of cells in a water phantom.

Using V79 Chinese hamster lung fibroblast cells grown in culture we have examined the lethal effects of fast neutrons from the Fermilab therapy facility as a function of depth in a water phantom. Exposures and dosimetry were performed from 3 to 24 cm deep in the phantom along the central axis of the neutron beam, using various collimator configurations. The results indicate that the relative biological effect (RBE), using 60Co gamma rays as the standard radiation, varies with depth in the neutron beam. Starting from d-max (approx. 3 cm), the RBE appears to decrease continuously with depth. At 24 cm deep, the relative effectiveness is 10-15% lower than at 3 cm deep. There appears to be no systematic variation of relative effectiveness with shape or size of collimator. If a hydrogenous filter is added before the beam passes into the water phantom, the variation with depth is greatly reduced.

Animals↗
PubMedDate not supplied

Frequency of occurrence of various nuclear reactions when fast neutrons (approximately less than 50 MeV) pass through tissue-equivalent material.

Calculated results are presented for the frequency with which various partial nuclear reaction cross sections are utilized when fast neutrons (approximately less than 50 MeV) are transported through a tissue-equivalent phantom to obtain an indication of which cross sections are of most importance for radiotherapy applications and are therefore in need of experimental verification.

Fast Neutrons↗
PubMed1984

Fast neutrons in the treatment of head and neck cancers: the results of a multi-centre randomly controlled trial.

The results are presented of a multi-centre randomly controlled trial of fast neutron irradiation and mega-voltage X-rays in the treatment of patients with locally advanced squamous cell carcinoma of the head and neck region. No significant difference was observed in local tumour control rates. Salvage surgery was performed in a similar number of patients in the two groups. Late morbidity was also similar in the two treatment groups. Patients in a subgroup with cancer of the larynx treated by photons had a significantly better survival than those in the neutron treated group.

Aged↗
PubMed1996

In vivo neutron activation analysis of sodium and chlorine in tumor tissue after fast neutron therapy.

In 12 patients with recurrences and metastases of different primaries (head and neck cancer, breast cancer, malignant melanoma, and osteosarcoma) who were treated with reactor fission neutrons the photon emission of irradiated tissue was measured after each radiotherapy fraction. Spectral analyses of the decay rates resulted in data for the exchange of sodium (Na) and chlorine (Cl) between the irradiated tissue and the body. About 60% of Na and Cl exchanged rapidly with a turnover half-life of 13 +/- 2 min. New defined mass exchange rates for Na and Cl amount to an average of 0.8 mval/min/kg of soft tissue. At the beginning of radiotherapy the turnover of the electrolytes in tissues with large tumor volumes was about twice that in tissues with small tumor volumes. Depending on the dose, neutron therapy led in all cases to variation in the metabolism. A maximum of Cl exchange and a minimum of Na exchange occurred after 10 Gy of neutrons (group of six previously untreated patients) or after 85 Gy (photon equivalent dose) of combined photon-neutron therapy. A significant increase in non-exchangeable fraction of Na from about 40 to 80% was observed in three tumors after a neutron dose of 10 Gy administered in five fractions correlated with a rapid reduction of tissue within 4 weeks after end of therapy. These results demonstrate for the first time the local response of the electrolyte metabolism to radiotherapy.

Chlorides↗
PubMed1999

Chromosomes participating in translocations typical of malignant hemoblastoses are also involved in exchange aberrations induced by fast neutrons.

Repeated triple-color fluorescence in situ hybridization was used for the detection of exchange aberrations among 10 selected chromosomes of human lymphocytes irradiated with three doses of fast neutrons with a mean energy of 7 MeV. In each hybridization two different pairs of chromosomes were stained. Defined stage positions of metaphases on a slide were stored on a hard disk and an automatic scan of images according to these positions was performed after six successive hybridizations. In this way we obtained six different images of the same metaphase with differently stained pairs of chromosomes and centromeres. The comparison of these images enabled the identification of mutual exchanges between chromosomes 1, 2, 3, 4, 8, 9, 12, 14, 18 and 22. The frequencies of exchanges were not linearly proportional to the molecular weight of interacting chromosomes. The most significant were exchanges between chromosomes 14/18, 14/8, 18/8, 8/3, 1/14, 1/8, 3/18, 3/14 and 9/22. The results indicate significant interactions between chromosomes involved in translocations in B-cell non-Hodgkin's lymphoma and chronic myeloid leukemia. We propose that the reason for the high frequency of exchanges between these chromosomes is their proximity in the cell nucleus. It may also be one of the reasons for the induction of specific translocations leading to malignant transformation of cells.

Cell Transformation, Neoplastic↗
PubMed1977

Fast neutron effects on multicell spheroids.

Accumulation and repair of neutron damage was measured using multicell spheroids irradiated with neutrons at the Hammersmith Cyclotron. A relative biological effectiveness (RBE) of about 1.5 (ratio of Do values) was found for aerobic single cells or small spheroids. Small spheroids accumulated more sublethal neutron damage than single cells, as indicated by a wider shoulder on the survival curve. However, neither single cells nor spheriods repaired sublethal damage when two doses of neutrons were separated by six hours or less. A "therapeutic gain" was observed for larger spheroids containing hypoxic cells, due to an increased RBE of fast neutrons for hypoxic cells amounting to about a factor of two.

Animals↗
PubMed1981

Microdosimetric investigations on collimated fast neutron beams for radiation therapy: II. The problem of radiation quality and RBE.

The correlation between radiation quality and cellular RBE of a mixed n-gamma field produced by a collimated fast-neutron beam produced by the bombardment of 14 MeV deuterons on Be in a water phantom is investigated. The microdosimetric parameters yF and YD are used for a physical description of the local distribution of radiation components. On the basis of the dose fractions of these components, the dependence of RBE on depth is calculated and is compared with experimental RBE data. Outside the beam centre, it is shown that the microdosimetric parameter y can be used for estimates of local changes of RBE, if particular conditions for the absorbed dose and for the range of neutron energies are met. The spatial distributions of y for the mixed radiation changes in RBE for equal absorbed doses of 1 Gy are at maximum 10% and thus perhaps negligible.

Cells, Cultured↗
PubMed1995

Morphological changes in rat's brain choroid plexus after exposure to low doses of high energy oxygen ions, fast neutrons, and gamma radiation.

Ultrastructural and morphometrical changes in choroid plexus cells of the rat's brain in the delay period after irradiation with low doses of oxygen ions [= 300 MeV/nucleon], and fast neutrons [1.5 MeV], and gamma rays (Co60) were described. The applied irradiations provoked similar ultrastructural changes in choroid plexus cells; however, the obtained morphometrical data showed differing effects of these radiations, due to, probably, different mechanisms of their effect on the cells.

Animals↗
PubMed1984

Radiation Therapy Oncology Group Phase I-II study on fast neutron teletherapy for carcinoma of the bladder.

From June 1977 through March 1981, the Radiation Therapy Oncology Group sponsored a Phase I-II study (RTOG 77-05) on the use of fast neutrons for treating carcinomas of the urinary bladder. Patients entered on the study had Stage B1 (grade III or IV histology) or Stage B2, C, or D1 (any grade histology) disease. Thirteen patients received preoperative mixed-beam (neutron/photon) irradiation to 50 photon Gy-equivalent, and in 12 of these a cystectomy was performed in 4 to 6 weeks. The incidence of pathologic downstaging to Po was 58% in the cystectomy specimens. The projected survival at 30 months is 32%. Twenty-six patients were treated definitively with mixed-beam irradiation consisting of 50 photon Gy-equivalent to the pelvis followed by a 20 photon Gy-equivalent boost to the bladder itself. Eighteen of 26 patients (69%) achieved tumor clearance at some time during their follow-up but 8/18 (44%) of these ultimately exhibited some component of local failure. The projected survival at 30 months for this group of patients is 34%. However, the subset of patients with Stage B or C disease had a projected survival at 30 months of 60%. Four patients received definitive neutron irradiation alone and 3/4 achieved tumor clearance at some time during their follow-up. Actuarial curves are presented for patient survival and duration of local control, and results are compared with comparably staged patients treated with megavoltage photon irradiation. Treatment-related morbidity is also discussed.

Aged↗
PubMed1996

Fast neutron therapy in treatment of soft tissue sarcoma--the Berlin-Buch study.

From 1975-1994, 221 adult patients with a total of 232 radiation sites for soft tissue sarcomas were irradiated with fast neutrons with a mean energy of 6.2 MeV in Berlin-Buch/Dresden-Rossendorf. The tumour dose ranged between 6 and 12 Gy and was limited by the low dose penetration of the neutron beam. A local control rate of 66% was obtained. The local control was affected by the tumour differentiation, residual status and histological subtype. Severe fibrosis of the subcutaneous tissues occurred in 40% usually after 2 years. No serious general side effects occurred. To optimize neutron therapy, a high energy clinically-based cyclotron with a fully rotational gantry and a multileaf collimator should be utilized. It seems that patients with locally advanced and well differentiated sarcomas can benefit from this therapy.

Adolescent↗
PubMed2004

Absolute dosimetry in a d(14 MeV) + Be fast neutron beam.

Since 1978, the Universitätsklinikum in Essen operates a d(14 MeV) + Be fast neutron beam for patient treatment. Dosimetric studies were performed in a rectangular 40 x 40 mm2 neutron/photon field using a transportable water calorimeter, which had been developed at the Physikalisch-Technische Bundesanstalt. The water calorimeter allowed small dosimeters to be directly calibrated in units of absorbed dose-to-water in a cylindrical phantom of 50 mm in diameter. Also, the twin detector method was applied in order to determine the photon and the neutron dose separately. By making use of a calibrated ionization chamber, the absorbed dose-to-water calibration in the cylindrical water phantom was transferred to a water phantom, a cube 300 mm on a side. Experiments and Monte Carlo calculations covering the neutron producing target, the collimator and the influence of the water calorimeter on the spectral neutron fluence at the measurement position allow the relative uncertainty of the absorbed dose-to-water determination to be reduced to 2.6% (1 SD). This direct absorbed dose-to-water determination by calorimetry has shown that the treatment planning system underestimates the physical dose to tissue by 9%. For clinical purposes, the statement of the prescribed dose had to be increased by 9% in order that the absolute absorbed dose remains constant and that the same biological endpoints are reached.

Boron Neutron Capture Therapy↗
PubMed1983

Combined effects of fast-neutron irradiation and subcutaneously applied carbon tetrachloride or chloroform in C57Bl6 mice.

Male and female C57Bl6 mice received a single whole-body dose of irradiation with 170 rad or 330 rad of fast neutrons. Nine weeks later they were given a single subcutaneous injection of carbon tetrachloride or chloroform. Chloroform did not influence the occurrence of tumours, but carbon tetrachloride markedly increased the incidence of radiation-induced liver carcinomas.

Animals↗
PubMedDate not supplied

[Effectiveness of a fast neutron beam to induce DNA damage in Ehrlich ascites carcinoma cells irradiated in a aqueous phantom].

The study of damages to DNA molecules of Ehrlich ascites tumor cells exposed in water phantom to fast neutron beam (mean energy of 6 MeV) showed that changes in the extent of DNA injury did not correlate with the absorbed dose distribution at the phantom depth of 8-12 cm, and also that the dose-response function in the phantom was different from that obtained upon irradiation of cells in the air.

Animals↗
PubMedDate not supplied

[Development of radiation injuries and recovery processes in the hematopoietic tissue of mice after repeated exposure to fast neutrons and gamma-irradiation].

A study was made of the number of CFUs and karyocytes in thigh bone and the concentration of functional cells in the peripheral blood of mice subjected to fast neutron- and gamma-irradiation four times at a 60-day interval (210 cGy per fraction). The regenerating potential decreased and the half-recovery time T1/2 increased in the haemopoietic tissue as the number of fractions and total absorbed dose increased. The dependence of T1/2 on the equivalent radiation dose was as follows: T1/2 = T1/2(0)e0.0009D.

Animals↗
PubMed1975

First results of a randomized clinical trial of fast neutrons compared with X or gamma rays in treatment of advanced tumours of the head and neck. Report to the Medical Research Council.

Results of the first randomized clinical trial to compare the effects of fast neutrons and those of x or gamma rays (photons) in treating patients with advanced tumours of the head and neck are reported. In 37 out of 52 patients treated with neutrons and 16 out of 50 treated with photons the local tumour completely regressed; the tumour later recurred in nine of the 16 photon patients but in none of the 37 neutron patients. The advantages to the neutron-treated patients were seen in tumours of well and poorly differentiated histology and in each site. Complications after treatment did not differ significantly between the groups. Despite these substantial differences in local control of the tumour there were no significant differences in mortality between the series. A detailed study of the effective doses and the response of tumours and normal tissue in each series indicated that the improved results from neutron therapy were due to differences in the biological quality of the beam and not to the rather higher average effective dose in the neutron series. To assess the long-term effects of neutron treatment patients in earlier stages of disease and with smaller tumours should be included in the next phase of the trial.

Clinical Trials as Topic↗