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PubMed1988

Therapeutic gain factors for fractionated radiation treatment of spontaneous murine tumors using fast neutrons, photons plus O2(1) or 3 ATA, or photons plus misonidazole.

Therapeutic gain factors (TGFs) have been determined for three spontaneous tumors of the C3H mouse treated by photons + normobaric oxygen (O2(1) ATA), photons + hyperbaric oxygen (O2 3 ATA), photons + misonidazole, or fast neutrons. The tumors were early generation isotransplants of spontaneous tumors: MCaIV, a mammary carcinoma; FSaII, a fibrosarcoma; and SCCVII, a squamous cell carcinoma. The tumors, transplanted to the right leg, were 6 mm at start of treatment. Normal tissue responses studied were acute reaction of normal skin (all treatment modalities) and LD50 following irradiation of the upper abdomen (in test of photons + O2 at 1 or 3 ATA). Thus both the tumor and normal tissues would be classified as "acute responding." All subject tissues were at congruent to 34.5-35 degrees C at irradiation. Treatments were based on d(25)Be or p(43)Be fast neutron beams, 60Co and 137Cs photon beams. Treatments were given in 5 or 15 equal doses in 5 days. For photon treatments, TGFs (air/O2 3 ATA) were substantially and significantly larger than 1 for all three tumor systems treated at small or large doses per fraction when related to skin or abdominal tissue responses. The TGFs (air/O2 1 ATA) were greater than 1 at small doses per fraction for MCaIV and FSaII for skin as the normal tissue; the TGFs for all three tumors and at all doses per fraction would be greater than 1 when related to upper abdominal tissues. TGFs (O2 1 ATA/O2 3 ATA) for photon irradiation greater than 1 were found only for SCCVII and that obtained for both large and small doses per fraction. Misonidazole achieved impressive TGFs (air/air + miso or air/O2 1 ATA + miso); the drug was tested only at 10-12 Gy/fraction and relative to skin. RBEs(FN) for the three tumors were lower at 1.5-2 Gy(FN)/fraction than at 5-6 Gy(FN)/fraction, i.e. the opposite to that reported for normal tissue (RBE increases with decreasing dose per fraction). A TGF (relative to skin reaction) greater than 1 for fast neutron therapy was found only for SCCVII when treated at large doses/fraction; this was true for air or O2 1 ATA conditions.

Animals↗
PubMed1983

[Fractionated irradiations of the normal rabbit lung with fast neutrons or photons].

115 rabbits were irradiated with our usual fractionation scheme, and the dose effect curves for fast neutrons and photons (60Co) were determined with respect to pneumonitis and pulmonary fibrosis, respectively. On comparison of the radiogenic alterations three months after therapy, the relative biological effectiveness calculated by means of these dose effect curves was 2,9 for the fast neutrons. Furthermore, the authors tested the conformity of some clinical examination methods such as X-ray, scintigraphy and computed tomography with histological findings of pneumonitis and pulmonary fibrosis, respectively. In this regard, computed tomography was superior to the other examination methods.

Animals↗
PubMed1989

Fast neutron radiation for inoperable and recurrent salivary gland cancers.

The current standard treatment of salivary gland cancers consists of surgical resection, with or without postoperative low linear energy transfer (LET) radiation, resulting in high locoregional control rates. However, tumor control prognosis is poor when conventional radiation is used alone for advanced, inoperable cases. An extensive review of the world's literature on fast neutron irradiation for inoperable, unresectable, or recurrent malignant salivary gland neoplasms is presented and compared with the experience using conventional low LET radiotherapy. The pooled data indicate a locoregional control rate of 67% for fast neutrons versus 25% for photons and/or electrons in the treatment of such advanced disease. The radiobiological rationale supporting this observed increase in tumor control is discussed. The overall significant late complication rate is 19%, but several suboptimal treatment factors were present that contributed substantially to the reported toxicity. With the modern machines and treatment techniques now available, the evidence overwhelmingly supports the role of fast neutron radiation as the treatment of choice for inoperable and recurrent salivary gland cancers.

Energy Transfer↗
PubMed2004

Cisplatin enhances the cytotoxicity of fast neutrons in a murine lymphoma cell line.

The utilization of high linear energy transfer (LET) radiations, such as fast neutrons or carbon ions (hadrontherapy), offers promising perspectives in radiotherapy. While it is well known that by combining radiotherapy and chemotherapy, important therapeutic advantages can be obtained to cure cancer, there have been, so far, very few investigations on the effects of treatments combining an irradiation with high-LET particles and cancer drugs. The present study was therefore undertaken to examine the effects of exposure to 65 MeV fast neutrons combined with cisplatin in a murine T cell lymphoma (RDM4) in vitro. The cells were irradiated at doses ranging from 2 to 8 Gy without or with addition of cisplatin shortly before the irradiation, at concentrations between 0.3 and 12.5 micro M. These treatments were applied concomitantly. Proliferation and apoptosis were assessed at different time intervals thereafter. The combination of irradiation with cisplatin was found to be more cytotoxic than either treatment alone. Furthermore, the cytotoxicity induced by this cotreatment resulted not only from apoptosis but also from other forms of cell death.

Animals↗
PubMed1997

A new fast-neutron source for radiobiological research.

A biomedical cyclotron facility primarily dedicated to radionuclide production has been extended by the addition of an experimental fast-neutron source for radiobiological and biophysical studies. Several beams of fast-neutrons with different average energies and LET distributions can now be provided. The neutrons are produced by bombarding berryllium targets with 18-32 McV protons or 8.7-15 MeV deuterons from our K = 32 negative-ion cyclotron. Average neutron energies range from approximately 4 to 15 MeV. Doses at maximum build-up vary from 0.24 to 1.85 cGy microA-1 min-1 at 1 m SSD, i.e. approximately 55 cGy min-1 at 30 microA of proton current at maximum energy. The design of the facility and some dosimetric results are presented.

Cyclotrons↗
PubMed1995

Fast-neutron therapy in advanced head and neck cancer: a collaborative international randomized trial.

PURPOSE: To compare the efficacy of fast-neutron radiotherapy with that of conventionally fractionated photon therapy in the management of patients with locally advanced squamous cell carcinoma of the head and neck. METHODS AND MATERIALS: Patients with Stage III or IV disease were randomized to receive either 20.4 Gy/12 fractions/4 weeks of neutrons or 70 Gy/35 fractions/7 weeks of photons (control). Between April 1986 and March 1991, 178 patients were entered, 169 of whom were eligible for analysis. The treatment arms were balanced for age, stage, and performance status, but not for primary site of origin. RESULTS: Complete response occurred in 70 and 52% with neutrons and photons, respectively (p = 0.006). Local regional failure at 3 years for all patients was 63% for neutrons and 68% for photons. Actuarial overall survival curves were virtually identical in both study arms, falling to 27% at 3 years. Acute toxicity was similar in the two arms, but late grade 3-5 toxicity was 40% with neutrons compared to 18% with photons (p = 0.008). CONCLUSION: Although the initial response rate was higher with neutrons, permanent local control and survival were not improved, and the incidence of late normal tissue toxicity was increased. As a result, fast-neutron therapy for advanced squamous cell carcinoma of the head and neck can only be recommended for patients in whom the logistic benefit of treatment in 12 sessions over 4 weeks outweighs the increased risk of late toxicity.

Adult↗
PubMed1996

Fast neutron therapy of bronchus carcinoma: the pooled results from two European centres.

The Berlin-Buch and Heidelberg centres used fast neutron therapy in bronchial carcinomas. The neutron source was a cyclotron in Berlin-Buch/Rossendorf and a d-t generator in Heidelberg. Three hundred twelve patients with inoperable bronchial carcinoma were treated with fast neutron therapy alone or in combination with photons. The results were then compared with those obtained from 594 patients treated only with photons. Altogether, 788 were treated in Berlin-Buch and 188 in Heidelberg. The results suggest that neutron therapy for bronchial carcinoma can be a good alternative in curative and palliative situations in the early stages.

Adult↗
PubMed2000

Ex vivo determination of the effect of whole-body exposure to fast neutrons on murine spleen cell viability and apoptosis.

The effects of high-linear energy transfer (LET) radiations on lymphoid tissues and lymphocytes are not well understood. As a first approach to delineate these effects, the present work was conducted to assess the effects of high-LET radiations on murine spleen cells ex vivo and in vitro. BALB/c mice were irradiated whole-body with 65 MeV neutrons or 15 MV X rays at doses ranging from 0.2 to 3 Gy. Spleens were removed 1 day postirradiation and weighed, and single cell suspensions were prepared and cultured for several days. Apoptosis occurring in vitro was determined at different times by flow cytometry analysis of cells labeled with propidium iodide. It was found that irradiation with fast neutrons reduced spleen weight and cellularity to a greater extent than photons. Considering the spleen cellularity as end point, the relative biological effectiveness (RBE) of fast neutrons was 2. However, for both modes of irradiation, apoptosis of recovered spleen cells in vitro increased as a function of dose and the duration of culture. The level of apoptosis occurring at various times postirradiation was found to be identical for high- and low-LET radiations. Taken together, these results suggest that external as well as cellular factors might differentially modulate the sensitivity of lymphocytes to fast neutrons and photons.

Animals↗
PubMed1992

Nonlinear survival curves for cells of solid tumors after large doses of fast neutrons and gamma rays.

We have previously proposed that survival curves for cells of murine NFSa fibrosarcomas after exposure to fast neutrons might demonstrate curvature when the neutron doses reach a level high enough to cure the fibrosarcomas. We report here that this is the case. Murine NFSa fibrosarcomas growing in the hind legs of syngeneic mice were exposed to either gamma rays or fast neutrons. The tumors were removed and retransplanted into fresh recipients to obtain 50% tumor cell doses, from which the dose-cell survival relationship was constructed. Survival curves showed continuous bending down to 10(-7), and were well fitted using the linear-quadratic model. The alpha and beta values for neutrons were larger than those for gamma rays. When the surviving fractions at experimental TCD50 doses were calculated using these values, comparable figures were obtained for neutrons and gamma rays. The RBEs for neutrons were comparable for the TCD50 and TD50 assays. Neutron RBE was independent of dose within a range of 5-28 Gy. The capacity of the tumors to repair the damage caused by large doses of neutrons was identical to that for small doses of neutrons, indicating that cells retained the capacity to repair neutron damage irrespective of the size of the dose.

Animals↗
PubMed1981

Dose-effect relations for tumour control and complication rate after fast neutron therapy for pelvic-tumours.

The effects of fast neutrons and high-energy photons were analysed for tumour control and skin and bowel damage after treatment of bladder and rectal cancers. A combination of statistical models was used for this analysis. A steep dose-effect curve was found for local tumour control as well as for the risk of complications. Some estimates were made of RBE values for control of bladder tumour and for normal-tissue damage. The implication of these data for neutron therapy is discussed.

Dose-Response Relationship, Radiation↗
PubMed1994

Dosimetry characteristics of four fast neutron generators involved in RTOG interinstitutional clinical trials.

PURPOSE: To demonstrate the consistency of dosimetry data used for four fast neutron generators involved in inter-institutional clinical trials. METHODS AND MATERIALS: Central-axis dosimetry characteristics (field size dependence, percentage depth dose, beam modifier factors) at four institutions were measured by independent physicists from the Radiological Physics Center. These measurements were made in water with a single set of dosimetry equipment using tissue equivalent ionization chambers. Measurements were made with the chamber cavities filled with stationary air and flowing tissue-equivalent gas. All measurements were performed using techniques developed by the Radiological Physics Center for conventional radiotherapy equipment. The results of our measurements were compared to the data used by the institution to determine the consistency of patient doses reported to the Radiation Therapy Oncology Group. RESULTS: The agreement of the Radiological Physics Center and institution data is similar to what is typically found with conventional radiotherapy equipment. CONCLUSIONS: The doses reported by these institutions to the Fast Neutron Working Group of the Radiation Therapy Oncology Group are consistent, within accepted clinical criteria.

Fast Neutrons↗
PubMed2001

A fast neutron deletion mutagenesis-based reverse genetics system for plants.

A new reverse genetics method has been developed to identify and isolate deletion mutants for targeted plant genes. Deletion mutant libraries are generated using fast neutron bombardment. DNA samples extracted from the deletion libraries are used to screen for deletion mutants by polymerase chain reaction (PCR) using specific primers flanking the targeted genes. By adjusting PCR conditions to preferentially amplify the deletion alleles, deletion mutants were identified in pools of DNA samples, each pool containing DNA from 2592 mutant lines. Deletion mutants were obtained for 84% of targeted loci from an Arabidopsis population of 51 840 lines. Using a similar approach, a deletion mutant for a rice gene was identified. Thus we demonstrate that it is possible to apply this method to plant species other than Arabidopsis. As fast neutron mutagenesis is highly efficient, it is practical to develop deletion mutant populations with more complete coverage of the genome than obtained with methods based on insertional mutagenesis. Because fast neutron mutagenesis is applicable to all plant genetic systems, this method has the potential to enable reverse genetics for a wide range of plant species.

Arabidopsis↗
PubMed1990

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues. III. Effects on lung function.

The effect of single and fractionated doses of fast neutrons (42 MeVd----Be) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 +/- 0.94 for infinitely small X-ray doses per fraction.

Animals↗
PubMedDate not supplied

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

BACKGROUND: Adenoid cystic carcinomas (ACC) seem to have a better response to fast neutron irradiation than to photon beam therapy because of the higher relative biological effectiveness of neutron radiation. METHODS: Between 1986 and 1995, 72 patients with ACC of the salivary glands were treated in Münster with fast neutrons. The median age was 54 years. All the patients had either recurrent or macroscopic rest tumor prior to neutron therapy. The median total dose was 15.03 Gy. Median follow-up was 50 months. RESULTS: 39.1% of the patients achieved a complete remission and 48.6% a partial remission. The survival probability was 86% after one year, 73% after two years and 53% after five years. The recurrence-free survival was 83% after one year, 71% after two years and 45% after five years. CONCLUSION: Neutron beam therapy seems to have been an effective treatment in these selected patients.

Adolescent↗
PubMed1989

Fast neutron radiotherapy in the treatment of locally advanced adenocarcinoma of the prostate. Clinical experience and future directions.

The major clinical experiences using fast neutrons for the treatment of locally advanced prostatic carcinomas are reviewed. In all trials to date, there is evidence that treatment regimens employing a component of fast neutrons achieve results that equal or surpass those obtainable with conventional megavoltage external beam irradiation for comparable groups of patients. Late complications of neutron treatment have not exceeded the complication rate expected by photon irradiation. The structure of the current Radiation Therapy Oncology Group phase III randomized trial comparing neutron and photon treatment of patients with stages B2, C, and D1 disease is discussed.

Adenocarcinoma↗
PubMed1976

Sources of fast neutrons for radiotherapy.

There is currently great interest in the use of fast neutrons for radiotherapy. Although it is too early for the long-term effects to be known, the results so far are encouraging. Three types of fast neutron-producing devices are available: neutron generators, compact cyclotrons and large cyclotrons. For the requirements of radiotherapists the most suitable and practical source currently available is the reaction 9Be(d,n) in conjunction with a large cyclotron capable of accelerating deuterons to energies greater than 35 MeV.

Beryllium↗