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PubMed1990

[The reaction of tumors and normal tissues to therapy with fast neutrons from the U-120 cyclotron].

In the present information results of clinical studies are represented to show the effectiveness of therapy with 6.3 MeV fast neutrons in 45 patients with superficial tumors in head and neck area. The reaction of tumor and of normal tissue was studied in dependence on different physical and biological factors. Two variants of neutron therapy planning were estimated by means of mathematical models of a factor of time-dose-fractionation for neutron (TDFN) from clinical point of view. Results of changes in oxygen-tension within the tumor are represented in 20 patients with metastases in cervical lymph-nodes during neutron therapy. The obtained data show a correlation of regression and reoxygenation rate of the tumor to its initial volume. The reaction of the tumor in therapy with fast neutrons was studied in dependence on its morphological structure. Complete regression of epidermoid and nonepidermoid cancer types was seen in 42 or 89% of the cases. With corrections for adipose tissue and the extent of dose fraction of fast neutrons the clinical test of the mathematical model of TDFN-factor made discernible that the reaction of normal tissue can be prognosticated quite exactly by means of this model in neutron therapy.

Adult↗
PubMed1999

Results of fast neutron therapy of adenoid cystic carcinoma of the salivary glands.

INTRODUCTION: Patients with adenoid cystic carcinoma (ACC) of the salivary glands in the head and neck region have been reported to benefit from neutron radiotherapy according to significant clinical experience. A prospective clinical trial on the efficacy and treatment related morbidity of fast neutron radiotherapy was performed between 1986 and 1995 at the (d + T) 14 MeV neutron generator in Münster. MATERIAL AND METHODS: 72 consecutive patients with ACC were treated with fast neutrons, 66 after surgery, 6 for primarily unresectable disease, 43/66 for macroscopic residual disease, 23/66 for unresectable recurrent disease. 45/72 tumors were localized in the minor, 27 in the major salivary glands. T-stage was in 13 pts T2, in 33 T3, in 26 T4; positive nodes were in 10 pts, M+ in 15 pts. Mean tumor volume was 89 cm3. Neutron therapy was 15.03 Gy in 3 weeks with 1.67 Gy per fraction three times per week. Individual computer assisted treatment planning was performed based on CT and/or MRI, using bolus material if necessary. Target volume was the macroscopic tumor volume with a generous safety margin. RESULTS: Complete response was achieved in 28 pts, partial response in 35 pts. Local control was observed in 73.4% after a mean observation period of 36 months. Overall and recurrence free survival was 85%/81% at two years, and 58%/53% at 5 years (Kaplan-Meier). In univariate analysis tumor volume (> 100 cm3), distant metastases, histologic subtype (solid) and neutron dose (< 15 Gy) turned out to be significant parameters for predicting outcome, in multivariate analysis tumor volume and histologic subtype remained the only significant parameters. Acute morbidity was grade III/IV (EORTC/RTOG) in 6% for skin (desquamation), in 4% for mucosa (ulceration), late morbidity (grade III/IV) in one patient with local temporal brain necrosis. CONCLUSION: According to this experience and taking into account the so far collected experience, fast neutron radio-therapy remains the treatment of choice for large and unresectable primary and recurrent ACC, and residual disease after surgery.

Adolescent↗
PubMed1987

[Fast neutron radiotherapy in the treatment of limb-salvage surgery in patients with osteosarcoma].

Preoperative radiotherapy and systemic chemotherapy are effective for reducing the size of a tumor and rendering it resectable. The results achieved with systemic chemotherapy are ultimately reflected in improved survival. Moreover, limb-saving procedure in the treatment of osteosarcoma has become possible with rationality in carefully selected patients. Since 1975, 38 patients with osteosarcoma within an age range of 5 to 56 years, (average 17.9 years) have been treated by fast neutron radiotherapy, systemic chemotherapy and limb-salvage surgery. Twenty-two of these 38 patients underwent en bloc resection of the femur, eight resection of the proximal tibia and five resection of the proximal humerus. Only one of the 38 patients had evidence of local tumor recurrence and overall, 31 patients are currently alive without distant metastasis after 9 to 120 months follow-up. Preoperative fast neutron radiotherapy was employed and it was suggested that fast neutrons had a higher relative biological effectiveness and a greater therapeutic gain factor in comparison with X-rays. Fast neutron radiotherapy thus seems capable of playing a significant role in the treatment of osteosarcoma and is specifically useful for preservation of the affected limb.

Adolescent↗
PubMed1994

The response of quiescent cell populations in murine solid tumors to irradiation with fast neutrons.

5-bromo-2'-deoxyuridine (BUdR) was injected into SCC VII tumor-bearing mice intraperitoneally to label all proliferating tumor cells. The mice were irradiated with fast neutrons or x-rays. Immediately, or 24 h after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus frequency was determined using immunofluorescence staining to BUdR. The cells that were not labeled with BUdR could be regarded as the quiescent cells. The micronucleus frequency in total tumor cells was determined from the irradiated tumors that were not pretreated with BUdR. The difference in radiosensitivity between total and quiescent cells was markedly reduced with fast neutrons, especially at higher doses of radiation. Potentially lethal damage repair by total and quiescent cells was inhibited more strongly with neutrons than with x-rays. When using fast neutrons, the radiosensitivity of solid tumors depends on their heterogeneity less critically than for x-rays.

Animals↗
PubMed1985

[Comparative kinetics of the early repair of intestines and lung in mice after fast neutron and gamma-ray irradiation].

Early repair (Elkind) after d(50) + Be neutron and gamma irradiation is assessed by determining the additional dose Dr necessary to reach a given biological effect when a single fraction Ds is split into 2 equal fractions 2Di separated by a time interval "i". LD50 at 180 days after thoracic irradiation is used as an evaluation of late pulmonary tolerance; LD50 at 5 days after abdominal irradiation is used as an evaluation of early intestinal tolerance. Dr is reduced but still important after neutron irradiation as compared to gamma irradiation. For LD50/180, after fast neutron irradiation Dr reaches 66, 90, 64, 162, 195, 150 cGy for "i" = 1, 2, 3, 5, 4, 12, and 24 hours respectively; after gamma irradiation, Field and Hornsey reported Dr = 390, 530, and 376 cGy for "i" = 2, 6, and 24 hours respectively; after neutron irradiation, they reported Dr = 190 cGy for "i" = 24 hours. For LD50/5, after fast neutron irradiation, Dr = 14, 45, 43, and 133 cGy for "i" = 1,5, 3,5, 5,5 and 24 hours respectively. Early repair is faster after gamma irradiation: Dr reaches a maximum for "i" = 3-4 hours. For neutrons, Dr reaches its maximum at 24 hours for both criteria.

Animals↗
PubMed1975

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↗
PubMed1992

Visualization of 3-D treatment plans with fast neutrons.

The treatment planning for radiotherapy with fast neutrons requires modifications of the planning systems used for photons. The neutron- and photon-component of the treatment fields must be determined and can then be used for separate calculations. The corrections for inhomogeneities are performed by use of attenuation coefficients and the corresponding corrections for changes in the kerma. The treatment planning system MEVAPLAN (Siemens) was modified to follow these requirements. Thus treatment planning for 14 MeV DT-neutrons could be performed. The multiplanar option is used to calculate 3D-dose distributions based on up to 40 serial CT slices. The generated three-dimensional dose matrix and the CT data are transferred via magnetic tape to the visualization system VOXEL-MAN developed at the University Hospital of Hamburg. This system uses a ray casting algorithm based on the generalized Voxel-model to display detailed 3D-images of human anatomy together with the calculated dose distribution. Different treatment plans for neutrons and photons are calculated and visualized. Various manipulations of the data-sets are displayed to improve the critical examination of the simulated dose distribution and to discern the quality of treatment techniques.

Fast Neutrons↗
PubMed1980

The isocentric fast neutron therapy facility at Edinburgh.

A second fast neutron beam for radiotherapy has been brought into operation at the Western General Hospital, Edinburgh. This beam is isocentrically mounted and can be rotated through +/- 120 deg from the vertical. Neutrons are produced by bombarding a thick beryllium target with 15 MeV deuterons. The provision of an isocentric facility enables some of the problems associated with poor beam penetration to be alleviated. The physical features of the isocentric facility are described with particular reference to the shielding and the methods employed to overcome problems of neutron activation. Both the prompt radiation leakage and the induced activity have been measured. It has been found that for the first eight months of operation the whole body dose-equivalent to radiographers was approximately 6 microSv (0.6 mrem) per patient treated. Dosimetry associated with the facility is discussed and an example of a seven field treatment plan for a bladder is presented.

Dose-Response Relationship, Radiation↗
PubMed1977

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↗
PubMedDate not supplied

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↗
PubMed1981

Dose--effect relationships, r.b.e. and split-dose effects after gamma-ray and fast neutron irradiation of protoplasts from wild Nicotiana species.

Protoplasts from a diploid Nicotiana species were used to investigate the effects of gamma-rays and fast neutrons. The damage was assessed by scoring the relative plating efficiencies. The effects of single acute doses, as well as fractionated doses, are described for both qualities of radiation. The dose--r.b.e. relationship, expressing the effectiveness of fast neutrons relative to gamma-rays as a function of dose, appears similar to that of most animal systems, with higher values in the region of lower doses. The fractionation of gamma-ray doses, with sufficiently long time intervals between split doses, allowed a substantial recovery, as known also for X-rays. On the other hand, the fractionation of a fast neutron dose into low single fractions markedly increased the biological effectiveness of the total dose. This could not be explained by cell progression during resting time intervals and necessitated an additional hypothesis, possibly involving other mechanisms in the specific action of low doses of radiation.

Dose-Response Relationship, Radiation↗
PubMed1987

Induction and subsequent repair of DNA damage by fast neutrons in cultured mammalian cells.

The induction and repair of DNA damage were studied by a DNA unwinding method in mouse L5178Y cells exposed to fast neutrons. DNA lesions induced by fast neutrons were classified into three types from their repair profiles: fast-reparable breaks (T1/2 = 3-5 min), slow-reparable breaks (T1/2 = 70 min), and nonreparable breaks. The repair rates of both fast-reparable and slow-reparable breaks were almost the same as those of corresponding damage induced by low-LET radiation. Neutrons induced a smaller amount of fast-reparable damage, an almost equal amount of slow-reparable damage, and a larger amount of nonreparable damage than those induced by equal doses of gamma rays or X rays. RBEs for fast- and slow-reparable damage were 0.3 and 0.9, respectively. The RBE for nonreparable damage was dose dependent and was 1.4 at the level of 100 breaks/10(12) Da DNA. Among the three types of lesions, only the nonreparable damage levels correlated with the linear-quadratic shape of the survival curves and with the enhanced killing effectiveness of neutrons (RBE = 1.7 at D0).

Animals↗
PubMed1987

The effects of a static magnetic field on DNA synthesis and survival of mammalian cells irradiated with fast neutrons.

The effects of a static magnetic field (0.75 T) on DNA synthesis and survival were examined with Chinese hamster V79 cells in cultures with and without fast-neutron irradiation. We found that the magnetic field applied alone for up to several hours did not cause a significant effect in either the rate of DNA synthesis or cell viability; the latter was assayed by colony formation. When cells were exposed simultaneously to the magnetic field and fast neutrons, the effects resembled those observed with neutrons alone. This was the case for both inhibition of DNA synthesis and cell killing. Cells irradiated first with neutrons followed immediately by 1 h of magnetic field exposure showed a dose-survival response curve indistinguishable from that of neutrons alone. These data suggest that the biological effect due to the magnetic field is negligible and that the presence of the magnetic field either during or subsequent to fast-neutron irradiation does not affect the neutron-induced radiation damage or its repair.

Animals↗
PubMed1979

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↗
PubMed2004

The fast neutron component in treatment irradiations with 12C beam.

Using 12C beams of 200 AMeV kinetic energy the production of secondary fragments from nuclear reactions in a thick water absorber (12.78 cm) was investigated. Fast neutrons and energetic charged particles (p-, d-, t-, a-particles) emitted in the forward hemisphere were identified by a BaF2/plastic-scintillation detector telescope. Neutron energy spectra were recorded at various angles using time-of-flight techniques. The neutron emission is forward peaked and the energy spectrum shows a broad maximum about half the energy per nucleon of the primary 12C ions. The total yield of fast neutrons emitted into the forward hemisphere integrated over the energy range of 25 to 500 MeV was found to be 0.43 +/- 0.1 per primary ion. The dose contribution of fast neutrons in patient treatments with carbon ions is estimated to be less than 1% of the total treatment dose.

Carbon↗
PubMed1992

Complications following fast neutron therapy for head and neck cancer.

Serious complications resulting from the use of fast neutrons to treat head and neck malignancies are reported in 38 patients. The average interval between treatment and onset of complications was 5.5 years. Significant airways obstruction, requiring a tracheostomy, occurred in two patients, and a gastrostomy or pharyngostomy was performed for intractable dysphagia in six. Eight patients developed osteoradionecrosis: carotid artery rupture occurred in three patients following surgery for residual or recurrent disease. Our experience suggests that complications following fast neutron therapy for head and neck tumours are more severe, more common and occur after a longer time interval than those seen following conventional radiotherapy. Subsequent surgery in the irradiated area is compromised by severely impaired wound healing. When radical surgery is necessary for residual or recurrent disease the entire volume of irradiated tissue must be removed if healing is to be achieved.

Airway Obstruction↗