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PubMed1984

The effect of sequential irradiation with X-rays and fast neutrons on the survival of V79 Chinese hamster cells.

V79 Chinese hamster cells have been exposed to X-rays or fast neutrons or to the two radiations given sequentially. Cells exposed to a priming dose of X-rays and then exposed immediately to a series of neutron doses regard the X-ray dose as equivalent to a neutron dose giving the same surviving fraction (iso-effective). If the cells are exposed to a neutron dose followed by X-rays the resulting survival is higher than would be obtained if the primary dose had been an iso-effective X-ray dose. However, it is lower than would be expected if the two radiations acted independently. The results imply that there is interaction between the damage caused by X-rays and fast neutrons. If the two radiations are given 3 hours apart they act independently.

Animals↗

PubMed1989

[3 years' experience of radiation therapy with fast neutrons on the V-120 cyclotron].

The paper discusses the results of treatment of 128 patients with head and neck cancer in whom fast neutrons (Y-120; approximately 6.2 MeV) were used as a single procedure or in combination with surgery. Tumors of different histomorphologic structure displayed unequal sensitivity to fast neutrons. Mean disease-free survival in patients with complete regression of tumor was 24 months following neutron therapy alone, 18.5 months after combined neutron-photon treatment and 5.5 months only in controls. Relapse rates were 20 and 15% in patients with pre- and postoperative neutron treatment, respectively, as compared to 52% in controls.

Adenocarcinoma↗

PubMed1976

Electron microscopic changes in rat parotid and submandibular glands subsequent total body irradiation with fast neutrons.

Female Sprague-Dawley rats wre irradiated with fast neutrons to study the radiobiologic effect on the parotid and submandibular salivary glands. Cytologic alternations were seen in the parotid tissues as early as 3 hours after exposure and peaked in both parotid and submandibular glands by the fourth postradiation day. The injury was manifest as damaged and sequestered intracytoplasmic organelles appearing as pleomorphic inclusions. The two types of glandular tissue showed similar morphologic alterations. No injury to blood vessels or other radiosensitive cells could be found.

Animals↗

PubMed2004

Application of semiconductors for dosimetry of fast-neutron therapy beam.

Two types of ion implanted miniature p-i-n diodes were tested in a d(48.5) + Be fast-neutron beam produced in the Detroit superconducting cyclotron. The increase in forward voltage drop caused by neutron-induced damage was correlated with neutron dose measured in a water phantom. The neutron and gamma dose components were predetermined using twin detector (Tissue-equivalent ion chamber paired with miniature Geiger-Müller counter) method. The increase in the voltage drop for 1 mA injection current was monitored together with the cyclotron beam target current, thus the differential voltage drop could be defined precisely for given radiation dose. The average neutron sensitivities of tested diodes were 1.284 +/- 0.014 and 0.528 +/- 0.058 mV per cGy. The miniature detectors can be utilised in characterisation of small radiation fields and in the regions of high dose gradient as well as for in vivo dosimetry of the patients undergoing fast-neutron therapy.

Equipment Design↗

PubMed2002

Effect of pre-exposure to beta rays of tritium on some biochemical parameters measured in organs of rats subsequently irradiated with fast neutrons.

The experiment examined biological responses produced by combined sequential exposure to low-level tritium contamination, followed by challenging irradiation with fast neutrons. Modifications of endogenous antioxidant potential of different organs in rats were discussed in relation to tissue radiosensitivity. Rats pre-contaminated to 7 cGy and 35 cGy have been additionally irradiated to 1 Gy with fast neutrons. Lipid peroxide level was determined in liver, kidney, small intestine, spleen, bone marrow, and plasma. Reduced glutathione (GSH) level and glucose-6-phosphate dehydrogenase (G6PDH) activity were determined in erythrocytes. An in vitro thymidine uptake assay was performed in isolated bone marrow cells. The lipid peroxide level decreased significantly only in liver and kidney from rats pre-exposed to 35 cGy. For small intestine and spleen, tissues of comparatively higher radiosensitivity, no induced radioprotection was observed, as reflected in the homeostasis of the lipid peroxides. The same behavior was observed in bone marrow, the most radiosensitive tissue studied. However, the bone marrow thymidine-incorporation assay revealed a possible adaptive-type reaction in rats pre-exposed to 35 cGy. We conclude that for radiosensitive tissues pre-exposure to chronic low doses of low linear energy transfer (LET) irradiation has no protective effect on their antioxidant status, whereas a protective effect is observed in radioresistent tissues.

Adaptation, Physiological↗

PubMed1984

Treatment experience with 15 MeV fast neutrons in the oral cavity and oropharynx.

All 86 patients with squamous cell carcinoma of the oral cavity and oropharynx treated with fast neutrons at the Mid-Atlantic Neutron Therapy facility at the Naval Research Laboratory (MANTA) from its inception in 1976 until closing in 1979, are reported. Patients generally had advanced disease or have failed or were failing conventional treatment prior to being treated at MANTA. The fixed horizontal beam parameters were suboptimal. Patients were treated by either neutrons alone or various combinations of neutrons and photons. In patients with T3 or T4 primary carcinomas treated with less than 2100 neutron rad, only 37% (3/11) had a complete response at the primary compared to 57% (24/42) treated to a higher dose. However, there was a significant evidence of radiation related complication. The latter was expected in a phase I/II trial of a new modality such as fast neutrons. Isocentric hospital based cyclotrons should offer some hope of improvement in the future.

Adult↗

PubMed1979

Delayed radiation necrosis of brainstem related to fast neutron beam irradiation: case report and literature review.

A 42-year-old man developed necrosis of the brainstem 10 months following fast neutron irradiation of a recurrent adenocystic carcinoma of the right submandibular salivary gland. The neoplasm had been diagnosed 15 years earlier. Neck dissection and several local excisions failed to control local extension, so that 7000 rad 4.8 MeV x-rays were administered. The right mandible and part of the tongue and palate were resected for recurrence and chemotherapy and transfer factor were given. Because of cranial neuropathy and erosion of the skull base, fast neutron radiation (2.080 rads) was administered five and one-half years after the x-ray therapy, but to a nonoverlapping field. Ten months later, rapidly progressive symptoms and signs of multiple cranial nerve palsies on the right side and left hemihypesthesia and hemiplegia appeared. Clinical manifestations of brainstem necrosis lasted 4 months. Postmortem examination demonstrated radionecrosis of pons and upper medulla, predominantly on the right side. This case illustrates the efficacy of neutron radiation in eradicating local carcinoma and also the serious complications of this therapeutic modality.

Adult↗

PubMed1994

Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial.

PURPOSE: To evaluate the effectiveness of fast neutron radiation therapy in treatment of locally advanced carcinomas of the prostate. METHODS AND MATERIALS: From April 1986 to October 1990, 178 patients were entered on a prospective, multi-institutional randomized study of the NCI-sponsored Neutron Therapy Collaborative Working Group. This trial compared external beam photon irradiation (7000-7020 cGy) with external beam neutron irradiation (2040 ncGy) for patients with high-grade T2 or T3-4, N0-1, M0 adenocarcinomas of the prostate. Eighty-nine patients were randomized to each treatment. Six patients were subsequently judged to be ineligible, leaving 85 photon and 87 neutron randomized patients eligible for analysis. RESULTS: With a follow-up time ranging from 40 to 86 months (68 months median follow-up) the 5-year actuarial clinical local-regional failure rate for patients treated with neutrons was 11%, vs. 32% for photons (p < 0.01). Incorporating the results of routine posttreatment prostate biopsies, the resulting "histological" local-regional tumor failure rates were 13% for neutrons vs. 32% for photons (p = 0.01). To date, actuarial survival and cause-specific survival rates are statistically indistinguishable for the two patient cohorts, with 32% of the neutron-treated patient deaths and 41% of the photon-treated patient deaths caused by prostate cancer (p = n.s.). Prostate specific antigen (PSA) values were elevated in 17% of neutron-treated patients and 45% of photon-treated patients at 5 years (p < 0.001). Severe late complications of treatment were higher for the neutron-treated patients (11% vs. 3%), and were inversely correlated with the degree of neutron beam shaping available at the participating institutions. Neutron treatment delivery utilizing a fully rotational gantry and multileaf collimator did not result in an increase in severe late effects when compared to photon treatment. CONCLUSION: High energy fast neutron radiotherapy is safe and effective when adequate beam delivery systems and collimation are available, and it is significantly superior to external beam photon radiotherapy in the local-regional treatment of large prostate tumors.

Adenocarcinoma↗

PubMed1988

Fast neutron radiotherapy for advanced malignant salivary gland tumors.

Thirty-two patients with inoperable, recurrent, or gross residual malignant salivary gland tumors received fast neutron radiotherapy at the University of Washington. Eleven patients were treated with low energy neutrons alone, four received a combined photon-low energy neutron treatment regimen ("mixed beam"), and 17 were treated with high energy neutrons alone. Patients treated for microscopic residual tumor after a surgical resection were excluded from this study. With a minimum follow-up period of one year, (maximum 12 years), the overall locoregional tumor control rate for the entire series was 81%. The 5-year locoregional tumor control rate was 69%. The overall 5-year survival rate was 33% (50% for T3 tumors and 0% for T4 tumors). Compared to results obtained with conventional photon and/or electron treatment for advanced salivary gland tumors, fast neutron radiotherapy appears to offer a significant advantage.

Adult↗

PubMed1992

Fast neutron radiation for recurrent pleomorphic adenomas of the parotid gland.

Between 1984 and 1989, six patients with recurrent pleomorphic adenomas of the parotid gland were treated with fast neutron radiotherapy. All of the patients in this series had one or more unfavorable prognostic features, which would predict suboptimal local tumor control rates with the utilization of standard surgical and adjuvant photon/electron radiation therapies. These prognostic features included multiply recurrent disease in three patients, known gross postoperative residual disease in one patient, extensive unresectable disease in one patient, and multiply recurrent disease plus gross postoperative residual disease in one patient. Patients had an average of three surgeries for recurrent adenomas before their neutron irradiation. The median period from the original diagnosis to the time of neutron treatment was 11 years, with a range of 1.3-32 years. With a median follow-up of 52 months, an overall local control rate of 100% was achieved. Only one grade III (European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group scale) late complication occurred secondary to the neutron irradiation. Similar to their malignant counterparts, benign salivary gland neoplasms appear to display excellent response and control rates to treatment with fast neutron irradiation. Neutron irradiation of pleomorphic adenomas should be considered an appropriate therapeutic approach in situations, such as recurrent disease and postoperative gross residual disease, where one may be concerned about potential local failures with the use of standard surgical and radiotherapeutic modalities. Neutron radiation also carries a low risk of facial nerve damage, a consideration that may argue for limiting the extent of surgical resection of recurrent disease.

Adenoma, Pleomorphic↗

PubMed2002

Sensitivity of whole human teeth to fast neutrons and gamma-rays estimated by L-band EPR spectroscopy.

This paper reports the first attempt to use L-band spectroscopy for estimating the sensitivity of whole teeth to fast neutrons and gamma-rays. Three teeth were successively irradiated first with fast neutrons with a wide energy spectrum (mean energy around 30 MeV) up to approximately 160 Gy and then with gamma-rays up to approximately 14 Gy. After each irradiation, L-band (approximately 1 GHz) EPR spectra of each whole tooth surrounded by the surface-coil resonator were recorded, yielding a single composite line principally due to CO2- and native radicals. The sensitivities are estimated by the slopes of the linear dose response curves of the dosimetric CO2- radicals. The ratios of the gamma/neutron sensitivities were found to be in the range 8-9 (+/- 2) for the three teeth.

Bicuspid↗

PubMed2001

Recoil proton, alpha particle, and heavy ion impacts on microdosimetry and RBE of fast neutrons: analysis of kerma spectra calculated by Monte Carlo simulation.

Fast neutrons (FN) have a higher radio-biological effectiveness (RBE) compared with photons, however the mechanism of this increase remains a controversial issue. RBE variations are seen among various FN facilities and at the same facility when different tissue depths or thicknesses of hardening filters are used. These variations lead to uncertainties in dose reporting as well as in the comparisons of clinical results. Besides radiobiology and microdosimetry, another powerful method for the characterization of FN beams is the calculation of total proton and heavy ion kerma spectra. FLUKA and MCNP Monte Carlo code were used to simulate these kerma spectra following a set of microdosimetry measurements performed at the National Accelerator Centre. The calculated spectra confirmed major classical statements: RBE increase is linked to both slow energy protons and alpha particles yielded by (n,alpha) reactions on carbon and oxygen nuclei. The slow energy protons are produced by neutrons having an energy between 10 keV and 10 MeV, while the alpha particles are produced by neutrons having an energy between 10 keV and 15 MeV. Looking at the heavy ion kerma from <15 MeV and the proton kerma from neutrons <10 MeV, it is possible to anticipate y* and RBE trends.

Alpha Particles↗

PubMed1994

Fast neutron radiation therapy. Results of phase III randomized trials in head and neck, lung, and prostate cancers.

The results of phase III trials comparing neutrons to photons for head and neck squamous cell cancers, non-small cell lung cancers, and prostate adenocarcinomas are reviewed, with emphasis given to the most recent U.S. National Cancer Institute sponsored randomized clinical studies in which fast neutrons were delivered using modern, hospital-based, high-energy, isocentric-capable cyclotrons. In locally advanced squamous cell head and neck cancers, neutrons showed no convincing advantage over photons. Fast neutron radiotherapy may have provided a therapeutic benefit in selected patients with inoperable non-small cell lung cancers. For locally advanced prostate adenocarcinomas, neutron therapy resulted in significantly superior clinical and histological loco-regional tumor control, which may translate to improved survival with additional follow-up. In general, severe late complications were more frequent with neutrons, especially in patients treated on older physics laboratory-based equipment. Even with modern state-of-the-art neutron generators, careful beam collimation and treatment planning are required to minimize side effects.

Adenocarcinoma↗

PubMed1986

The Amsterdam fast neutron therapy project: a final report.

In the period from February 1975 through September 1981 a total of 435 patients received radiotherapy with the 14 MeV d + T neutron generator, hospital based in the Netherlands Cancer Institute (the Antoni van Leeuwenhoek Hospital). Preliminary data on clinical results were published during the past few years. In this paper a final report is given of the program. The results can be summarized as follows: The neutron generator fulfilled the criteria for clinical use, that is it was reliable and had the required minimal output of 10(12) neutrons s-1. However, the dose distribution was more comparable with a 250 kV X-ray machine than with a modern accelerator. A number of physical parameters of importance for clinical neutron dosimetry have been determined for our therapy unit. These data, as well as the results of dosimetry intercomparisons in which our institute participated, contributed in the drafting of a European protocol for clinical neutron dosimetry. Pilot studies were carried out on different tumor sites, including head and neck, brain, pelvis, soft tissue and pulmonary metastases. In many patients local tumor control was seen, however, often concomitant with severe complications, especially in deep seated tumors. Randomized clinical trials were carried out for head and neck tumors (in collaboration with some other European centers) and for inoperable bladder and rectal tumors. No significant difference was observed in local tumor control or late morbidity between photon and neutron irradiation for the head and neck tumors. Also the results for pelvic tumors failed to demonstrate an advantage for neutron therapy. In this study two neutron arms were used with different dose schedules. As could be expected a higher local control rate was noticed for the higher neutron dose group, but concomitant with a higher complication rate. From our experience we have to conclude that treatment with our fast neutron treatment facility did not result in a benefit over photon irradiation. It seemed that the differential effect between tumor and normal tissues is smaller with fast neutrons than with photons.

Evaluation Studies as Topic↗

PubMed1988

The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. I. Effects on the epidermis and dermal vascular/connective tissues.

The effects of fractionated doses of fast neutrons (42 MeVd----Be) on the early epithelial and later dermal response of pig skin have been assessed and compared with those after X irradiation. For the early epithelial reaction, i.e. moist desquamation, the relative biological effectiveness (RBE) of the neutron beam increased with the decreasing size of the X-ray dose/fraction. There was an experimentally observed upper RBE value of approximately 2.75 for X-ray doses/fraction of between 2 and 5 Gy. For the late reaction of ischaemic dermal necrosis the RBE was greater than 3.0 for X-ray doses/fraction of less than 3 Gy and, based on the assumptions made in the linearquadratic model of cell survival, an upper limiting RBE of 4.32 +/- 0.39 was calculated for infinitely small doses/fraction. These findings were compared with other radiobiological data and the conclusions drawn from the results of clinical trials. It was concluded that for the sparing of late effects in skin and subcutaneous tissues, relative to acute reactions, a relatively small number of fractions in a short overall treatment time may be optimal for fast neutron therapy.

Animals↗

PubMed1978

Clinical experience with fast neutrons in Amsterdam.

Since November 1972 a pilot study of fast neutron therapy has been carried out in Amsterdam at the Antoni van Leeuwenhoek Hospital (the Netherlands Cancer Institute). With a d + T machine almost 200 patients were treated in 2 years. In this paper the preliminary results will be discussed.

Fast Neutrons↗

PubMedDate not supplied

[Induction of mutations resistant to 6-thioguanine by fast neutrons in cultured Chinese hamster cells].

A study was made of induction of mutations, resistant to 6-thioguanine (TGr), and reproductive death of Chinese hamster cells after irradiation by fission-spectrum fast neutrons (mean energy of 0.75 MeV) with doses of 10-130 cGy. A high relative biological effectiveness (RBE) of fast neutrons was shown. The maximum RBE values (13-16) were within the dose range inducing minimum mutagenic and lethal effects. RBE decreased with the dose increase. Inspite of high mutagenic effectiveness of neutrons, estimated according to TGr mutation frequency per cell per dose unit, their relative mutagenic effectiveness, estimated per cell per one lethal event, did not substantially differ from that of X-radiation.

Animals↗

PubMed1982

Fast neutron beam radiation therapy in the United States.

Following a 30-year hiatus after Dr. Stone's work in the 1930's and 1940's, clinical trials with fast neutrons were restarted in the United States in 1972. Approximately 2500 patients have been treated with neutrons since that time. Three hundred and seven patients with squamous cell carcinomas of the head and neck were entered on an RTOG-coordinated randomized study comparing standard photon irradiation with mixed beam radiation therapy. No significant differences were noted in the local control, survival or complication rates. One hundred and sixty patients were entered on a randomized glioblastoma study. Although there were no significant differences in median survival, autopsy results showed greater tumor effect on the neutron-treated tumors. Twenty-six patients were treated for transitional cell carcinomas of the bladder with either preoperative mixed beam irradiation or mixed beam irradiation alone. Both the local control rates and survival rates compare favorably with photon radiation therapy. The future of fast neutron beam radiation therapy in the United States is discussed.

Brain Neoplasms↗