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Kermas for various substances averaged over the energy spectra of fast neutron therapy beams: a study in uncertainties.

Kermas for various substances averaged over the energy spectra of fast neutron therapy beams, as well as ratios of average kermas relative to muscle, were calculated in an attempt to estimate the uncertainties introduced in these quantities by the poor knowledge of the elemental kerma functions, actual neutron energy spectra, and composition of tissues and other materials. Average kermas have uncertainties of the order of 7%-25%, while for ratios of average kermas the uncertainties are of the order of 2%-5% for materials of clinical interest. It is concluded that the ratio of average kerma of muscle to A-150 tissue-equivalent plastic should be 0.93 +/- 0.03 for the new p + Be clinical neutron beams.

Adipose Tissue↗

[Comparative effectiveness of metronidazole, hyperglycemia and hyperthermia in irradiation of Ehrlich carcinoma with fast neutrons].

A study was made of a possibility of the modification of the effects of fast neutrons (with the mean energy of about 6 MeV.) by local hyperthermia (HT), short-term induced hyperglycemia (STIH) and metronidazole (MZ). The study was conducted in vivo on intramuscularly transplantable ascitic mouse Ehrlich's carcinoma. The dose-effect relationship built up in different time after the day of irradiation, was considered in parallel with the time course of tumor growth; regression curves were obtained using computer. Using the value of 50% tumor growth inhibition and the ratio of areas under the model dose-effect curves as criteria of a degree of modification the authors have come to a conclusion that HT possesses the most noticeable intensifying effect.

Animals↗

Combined cyclotron fast-neutron and BCNU therapy in a rat brain-tumor model.

The combination of cyclotron fast-neutron radiotherapy with BCNU chemotherapy was compared to 137Cs gamma photon radiotherapy combined with BCNU in the 36B-10, F-344 rat-transplanted glioma model. Radiation and drug treatments were administered 7 to 8 days after intracerebral tumor implantation. Increase in animal survival time was used as the measure of the effectiveness of various treatment schedules. Single-dose neutron or gamma radiotherapy was tested on Day 7 over the ranges 0 to 900 rads and 0 to 2000 rads, respectively. This therapy produced increases in mean survival times up to 70% at the highest radiation doses. When BCNU (10 mg/kg body weight) was administered intravenously on Day 8, 1 day following radiotherapy, mean survival times were increased by an additional 35% to 50%, irrespective of the dose or type of irradiation. In contrast, by using the same radiation and drug doses but scheduling combined therapy trials so that BCNU was administered 1 hour before either neutron or gamma irradiation on Day 7, there was enhancement of the radiation effect by BCNU. Under these conditions, the maximum enhancement of the mean survival time was 70% to 75% in neutron-treated animals and 120% to 150% in gamma-treated animals. Treatment with BCNU 1 hour before or 1 day after neutron irradiation proved to be no more effective in proving the survival time of tumor-bearing animals than the drug similarly combined with conventional gamma irradiation.

Animals↗

Fast neutron irradiation for prostate cancer.

The purpose of this study was to summarize the progress made using fast neutron irradiation in the treatment of prostate cancer at Wayne State University between 1991 and the year 2001. The results of three Phase II studies and one Phase III st udy involving nearly 700 patients is summarized in this paper. The Phase II studies weredose finding studies looking at doses of 15, 9, 10, and 11 nGy, respectively. The randomized protocol was a study of sequence looking at the results of treating patients with neutron first versus neutron radiation last. The results demonstrated that the best combination of tumor control probabilities and normal tissue complications was found in a mix of approximately 50% neutrons and 50% photons. Thus, the standard doses become 10 nGy and 40 Gy of photons. The randomized trial demonstrated that the sequence has significant importance and the disease-free survival was 93% for patients treated with neutrons first versus 73% for patients treated with neutrons last. There was no difference in the rate of acute or chronic complications. Finally, an analysis was performed demonstrating which patients may best benefit from the use of neutron irradiation. It was shown that patients with one, two, or three adverse risk factors had a significant improvement in disease-free survival when part of the treatment included neutron radiation versus standard photon radiation alone. Neutron radiation can be delivered safely with effort to see that it is superior to that which can be achieved by conformal photon irradiation by itself. Future work will be done to expand the role of neutron radiation in other clinical disease sites.

Fast Neutrons↗

Fast neutron therapy clinical trials in the United States.

The National Cancer Institute (NCI) began supporting clinical fast neutron clinical studies in the United States beginning in the early 1970s using physics-based cyclotrons and linear accelerators at a number of locations and facilities. The early work pointed out the handicaps imposed by the limitations of horizontal beams and low energy neutrons. This, combined with some encouraging, clinical results using neutrons and photons in a mixed mode of therapy, prompted the NCI in 1979 to initiate a 10-year contract program to design, develop, and build hospital-based neutron therapy machines and to conduct phase III clinical trials. As we approach the end of the 10-year effort, three hospital-based neutron facilities are currently operational-at the University of Washington, Seattle; University of California at Los Angeles: and M. D. Anderson Hospital at University of Texas System Cancer Center, Houston. Phase III trials are in progress in four sites: head and neck, prostate, and lung tumors, and cancers of radioresistant histologies, such as melanoma, renal cell carcinoma, and sarcomas of the soft tissue and bone. The contractors will continue to receive limited NCI support to complete the clinical studies.

Clinical Trials as Topic↗

[Characteristics of chromatin breakdown in the rat thymus after exposure to fast neutrons and gamma rays].

A comparative study was made of the radiobiological aftereffects of the action of fast neutrons and gamma-rays on lymphoid tissues of rat thymus with a reference to a biochemical criterion of the interphase death of lymphocytes, i.e. the formation of polydeoxynucleotides (PDN). It was shown that the increase in the chromatin degradation was a function of dose of neutron- and gamma-radiation (up to 4 Gy). The dynamics of the PDN formation was similar with both types of radiation, but 4-6 h after neutron irradiation chromatin degradation was higher more pronounced. The RBE of neutrons varied from 3 to 2 with a radiation dose varying from 0.25 to 4 Gy.

Animals↗

Fast neutron beam radiotherapy of glioblastoma multiforme.

Twenty-one patients with glioblastoma multiforme were treated with fast neutron beam irradiation of the whole brain. Therapy was well tolerated up to calculated doses of 1.850 radn+y in 12-18 increments over 6 weeks. The survival rate 6 month after initiation of treatment was 62%, not significantly different from conventional photon therapy; average posttreatment survival appears to be shortened compared to photon therapy. No improvement or prolonged maintenance of existing neurologic function was observed. Autopsy findings in seven patients showed replacement of tumor by coagulative necrosis persisting at least 16 months posttreatment, paucity of tumor cells with infrequent mitosis, and suppression of macrophage response. These findings differ from those in conventionally irradiated patients. No treatment-related changes were documented by conventional gross and histologic studies of the irradiated brains distant from the tumors. Thus the deaths of patients in this study appear to be related to unexplained causes other than progressive growth of tumor.

Brain Neoplasms↗

Double strand-breaks and DNA-to-protein cross-links induced by fast neutrons in bacteriophage DNA.

Coliphage T7 was suspended in tryptone broth and exposed to a mixture of fast neutrons and gamma radiation. Plaque survival, double strand-breaks and DNA-to-protein cross-linkage were examined and the results compared with those found in phage exposed to gamma radiation alone. Neutral sucrose density sedimentation patterns indicate that neutron-induced double strand-breaks sometimes occur in clusters of more than 100 in the same phage and that the effeciency with which double strand-breaks form is about 50 times that of gamma-induced double strand-breaks. Neutron-induced protein-to-DNA cross-links probably also occur in clusters with enhanced efficiency relative to low LET radiation.

Coliphages↗

RBE in fast neutron therapy and in boron neutron capture therapy. A useful concept or a misuse?

In high-LET radiation therapy, radiation quality and radiation quality differences have to be taken into account and specified. In fast neutron therapy, an operational approach has been adopted which is based on the concept of "clinical RBE". The paper discusses the quantities of RBE (relative biological effectiveness), reference RBE and clinical RBE and their relationship and significance in radiation therapy. In particular, the difference between the well defined RBE in radiation biology and the clinical RBE which is based on the judgement of radiotherapists is elucidated and emphasized. The clinical RBE is based on the reference RBE and implicitly includes differences in physical selectivity of the irradiation beams and clinical experience. The particular aspects of radiation quality in boron neutron capture therapy (BNCT) are due to the poor penetration of the primary beam, the inhomogeneity of the spatial distribution of 10B nuclides in the irradiated tissue and the short range of the alpha-particles emitted after neutron capture in 10B. The related problems in accounting for radiation quality in BNCT and in the applicability of the clinical RBE concept are discussed.

Boron Neutron Capture Therapy↗

Transient and chronic neurological complications of fast neutron radiation for adenocarcinoma of the prostate.

The records of 132 patients participating in clinical trials using fast neutron (n = 94), mixed neutron and photon (n = 16), or conventional photon (n = 22) irradiation for primary management of prostatic cancer were retrospectively reviewed to assess treatment-related neurological complications. With a median follow-up of 14 months (range 1 to 101 months), 31/132 patients (26 neutron, 3 mixed beam, 2 photon) have experienced either sciatica beginning during or shortly after treatment, or diminished bladder or bowel continence that developed at a median time of 6.5 months following treatment. Sciatica responded to oral steroids and was usually self-limited, whereas sphincter dysfunction appears to be permanent. Pre-treatment risk factors for complications included a history of hypertension, diabetes, cigarette smoking or peripheral vascular disease, with 81% of affected patients having one or more risk factors compared with 55% of unaffected patients (p = 0.01). Seven patients have moderate (5) or severe (2) residual problems, all in the cohorts receiving neutrons (6/7) or mixed beam therapy (1/7).

Adenocarcinoma↗

Simulations of silicon microdosimetry measurements in fast neutron therapy.

Experimental silicon microdosimetry measurements were performed at a Fast Neutron Therapy facility. Monte Carlo based calculations of these measurements were made using the GEANT4 toolkit. Reasonable agreement between theoretical and experimental results was obtained and the contribution of elastic and inelastic reaction products to the final microdosimetric spectrum was determined.

Computer Simulation↗

Fast neutron therapy for soft tissue sarcoma.

Seventy-nine patients with soft tissue sarcoma were treated with fast neutron therapy at the Hammersmith Hospital, MRC Cyclotron Unit. Sixty-six of these, treated between 1971 and 1983 were assessable. The histology was reviewed and graded in 82% of cases and tumors divided into groups according to maximum diameter. In sixteen patients, who were irradiated following complete macroscopic removal of tumor, there was 94% local control and 86% survived 5 years. Of the 50 patients who had gross tumors present 62% were greater than 10 cm in diameter, and 20 were recurrent after previous radiotherapy or surgery or both. Sixty-eight per cent of gross tumors completely regressed and local control was 52%. The main cause of death was metastatic spread, and median survival was 63 months for Grade 1 patients, 9 months for Grade 2, and 7 months for Grade 3. Thus, there was a significant advantage to patients with Grade 1 tumor but little difference between Grades 2 and 3. Twenty-seven patients experienced late complications of treatment, 67% of which involved the skin predominantly and were related to the low energy of neutrons used. Seventeen of the 27 had received previous radiotherapy. Neutron therapy given in this dose and fractionation produced a higher local control rate than photon therapy, but complications were more frequent. Since these mainly involved the skin a lower level of complications may be anticipated using higher energy neutrons which will have a more even distribution of dose and lower skin dosage. Forty-eight per cent of patients developed metastatic disease, indicating the need for effective systemic therapy, especially in Grades 2 and 3 tumors.

Fast Neutrons↗

Wedge factor dependence with depth and field size for fast neutron beams.

The dependence of the wedge factors (WFs) on field size (FS) and depth for a fast neutron beam has been investigated. In a previous study (Popescu et al 1999 Med. Phys. 26 541), a method was presented that allows a simple and accurate way of calculating the wedge-factor dependence on FS and depth in the case of a photon beam. The validity of a similar approach is tested in the present study for neutron beam dosimetry. The clinical neutron therapy system at the University of Washington (UW) has a flattening filter assembly consisting of two filters: a small field filter and a large field filter. Despite this complication, the approach presented in Popescu et al (1999 Med. Phys. 26 541) can be used to describe the WF dependence on FS and depth (d).

Calibration↗

[Present status of high LET radiation therapy--fast neutron radiotherapy in Japan].

More than 1,900 patients of advanced and inoperable malignant tumor were treated with fast neutron radiotherapy using 30 MeV (d-Be) and 14 MeV (d-Be) beams at NIRS and IMS between 1975 and 1986. Protocols were largely nonrandomized. Some results have been obtained: 1) results with mixed beam studies for advanced squamous cell carcinoma of the uterine cervix have been equivocal compared with the photon controls. 2) some trends of local control have been observed in the trial of esophageal cancer, early cases of adenocarcinoma of the lung and malignant melanoma. 3) significant better results were observed in the pancoast type lung cancer and osteo sarcoma which was treated by the systemic multimodal treatment. It is concluded that neutrons are efficacious for certain specific tumor types owing to some biological effects, however the problem of inferior dose distribution was the weakness of neutron therapy at present.

Bone Neoplasms↗

Displacement correction factor for fast-neutron dosimetry in a tissue-equivalent phantom.

The displacement correction factor to be used for analysis of fast-neutron dosimetric measurements using air-filled EG and G tissue-equivalent ion chambers in a tissue-equivalent phantom has been investigated using the MANTA neutron radiotherapy beam generated by 35-MeV deuterons on a thick Be target. The displacement correction factor inferred from these measurements is 0.970 for the EG and G IC-17 (1.0-cm3) ion chamber, and is 0.989 for the EG and G IC-18 (0.1-cm3 ion chamber. This multiplicative displacement correction factor has no significant dependence on depth in the phantom or on neutron beam size.

Fast Neutrons↗

Evaluation of fast neutron teletherapy for advanced carcinomas of the major salivary glands.

This review analyzes the local control rate of fast neutron beam teletherapy for malignant salivary gland carcinomas compared to conventional photon irradiation at the same institution. Thirty patients with malignant parotid or submaxillary gland tumors were treated with either cobalt-60 (19 patients) or neutrons +/- photons (11 patients). The 19 photon-treated patients were historical controls. No advantage is found for neutrons in patients with tumors less than 3 cm where 100% local control was achieved with either modality. In patients with tumor masses 3-6 cm in size, neutrons demonstrated a possible advantage with a local control rate of 100% (followup, 7-18 months) compared to a control rate of 33% with conventional photon irradiation. Acute treatment-related morbidity was slightly greater in neutron-treated patients, but no long-term complications have been observed to date.

Evaluation Studies as Topic↗