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B G Douglas

Publications and source records attributed to B G Douglas.

At least 19 recordsLinked to original sources
PubMed1990

Preclinical evaluation of pions in vivo: experience at TRIUMF.

This paper describes the results obtained from in vivo studies of the pion beam at the TRI University Meson Facility (TRIUMF). The studies encompass work (from 1978 to 1986), designed to evaluate the RBE for early and late effects and to assess the importance of X-ray dose rate and treatment volume on these values. Results with early responding tissues, i.e. mouse and pig skin and mouse intestine indicate a pion RBE of about 1.5 in the clinically relevant dose per fraction range of 2-3 Gy. At these doses, RBE appears to be independent of the reference X-ray dose rate. However, at high doses per fraction, the RBE values become increasingly X-ray dose rate dependent. The induction of late effects by pions has been assessed by monitoring the late dermal response of pig skin; late fibrosis was not assessed in this study. The values obtained using the chosen endpoint indicate that the RBE is not significantly higher than that seen in any of the early responding tissues for pion doses as low as 2-3 Gy per fraction. The effect of increasing the treatment volume for pion therapy has been assessed using mouse intestine. The results show that for a constant field size, RBE decreases with increasing peak width. However, if peak width is held constant and field size increased, there is evidence for an increased RBE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Superfractionated radiotherapy in grade III, IV intracranial gliomas.

Preliminary results of superfractionation in the treatment of glioblastoma led to a randomized trial consisting of 76 patients. All patients received whole brain irradiation followed by a 1000 cGy boost to the primary site. Thirty-four patients received standard daily treatment to 4000 cGy, whereas 42 patients received superfractionated radiation, treating three times a day to a total dose of 4760 cGy. No significant difference was found between the 5-year survival of the superfractionated group and the standard treatment group. Early reactions were greater for superfractionation whereas late effects were less.

Adult↗
PubMed1987

The response of mouse epidermis to fractionated doses of pi mesons.

An extensive series of preclinical experiments are described in which the relative biological effectiveness (RBE) of pions from TRIUMF has been determined for mouse skin. To measure the RBE at both high and low doses per fraction, a range of fractionation schedules was used, with 1, 2, 4, 10, and 20 fractions. Because the pion dose rate is much lower than the dose rate of X or gamma-rays used in radiotherapy, two sets of reference X ray data were obtained: one at the same dose rate as the pions (15 cGy min-1), and another at the more conventional 150 cGy min-1. This allowed a "biophysical" RBE for equivalent dose rates and a "practical" RBE for preclinical evaluation to be calculated. The pion RBE was significantly higher for 20 small fractions than for fewer large doses. The absolute value of RBE depends upon the dose rate of the reference X ray treatments. The "practical" RBE increased from 1.05 at high doses to 1.45 at the smallest dose per fraction tested. The "biophysical" RBE for equivalent dose rates ranged from 1.20 at high doses to 1.5 for 20 fractions.

Animals↗
PubMed1986

Pions and pig skin: preclinical evaluation of RBE for early and late damage.

The skin of 50 pigs has been irradiated with negative pi mesons and with X rays in order to determine the RBE for early epidermal and later dermal damage. Late fibrosis was not studied. Four, 7, 9 and 10 fractions were used. An estimate of the RBE was made from the reactions on each pig for both early and late damage so that interanimal variability would be avoided. The data were also averaged to obtain mean dose response curves. There was no tendency for higher RBE's for late than for early skin damage. These pig studies have demonstrated an RBE of about 1.5 for early epidermal reactions and a slightly lower RBE (approximately 1.4) for later dermal damage in the same animals. This indicates that at doses of about 2.0 to 3.5 Gy pions, the medium wave skin damage is unlikely to be more severe than would be predicted from the early skin reactions and the accumulated clinical experience with X rays. However, if the trend to a steeper slope for the RBE versus dose per fraction for late injury is correct, as indicated by other published studies a relative increase in the late injury might be expected if much lower doses per fraction are used. The present clinical studies at Vancouver using 15 X 2.1 Gy pions indicate that an RBE of 1.5 is appropriate for epithelia, brain and colorectum.

Animals↗
PubMed1985

In vitro and in vivo studies of the TRIUMF pion therapy beam.

Patient treatments at TRIUMF (Tri-University Meson Facility, Vancouver, B. C.) use a moving spot raster scan technique where the pion range is modulated in depth for each position of the moving spot. The spot scans in a stepwise fashion and can produce any desired field shape. This approach provides very good dose uniformity across the treatment field and allows maximum flexibility in shaping the treatment volume. Survival of cultured cells has been used as a biological dosimeter to test the isoeffectiveness of the pion dose distributions, which must be shaped in depth to compensate for the depth-dependent LET distribution. Isoeffectiveness across the treatment field has also been verified using this system, which involves irradiating cells supported in a gelatin matrix. The response of pig skin to pion irradiation at TRIUMF has provided a check on the in vivo RBE for acute effects derived from our earlier studies with mouse foot. In addition, the pig skin reactions have been followed for several months to assess the later dermal response. The RBE of our pion beam relative to 270 kVp X rays is approximately 1.5 for both the acute epidermal and the later dermal responses.

Animals↗
PubMed1983

AIDS and sudden death.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Implications of the quadratic cell survival curve and human skin radiation "tolerance doses" on fractionation and superfractionation dose selection.

An analysis of early published multifraction orthovoltage human acute skin irradiation tolerance isoeffect doses is presented. It indicates that human acute skin radiation reactions may result from the repetition, with each dose fraction, of a cell survival curve of the form: S = e-(alpha D + beta D2) The analysis also shows no need for an independent proliferation related time factor for skin, for daily treatments of six weeks or less in duration. The value obtained for the constant beta/alpha for orthovoltage irradiation from these data is 2.9 x 10(-3) rad-1 for the cell line determining acute skin tolerance. A radiation isoeffect relationship, based on the quadractic cell survival curve, is introduced for human skin. This relationship has some advantages over the nominal standard dose (NSD). First, its use is not restricted to tolerance level reactions. Second, a modification of the relationship, which is also introduced, may be employed in the selection of doses per treatment when irradiation dose fractions are administered at short intervals where repair of sublethal injury is incomplete.

Cell Survival↗
PubMed1982

Superfractionation in glioblastoma multiforme--results of a phase II study.

A sequential series of 30 patients who were referred to a cancer treatment hospital with glioblastoma multiforme were treated with superfractionated cobalt 60 gamma radiation, three treatments per day, 100 rad per fraction. Their survival was compared to that of a historical group of 90 patients who had been referred for the same disease. Survival of the study patients was significantly longer than the historical patients, both for those who underwent resection (48.6 weeks median survival vs. 35.1 weeks), and for those who did not (35.1 weeks vs. 11.7 weeks). A retrospective survey of the historical group led to the following conclusions about this group: 1. Survival for patients who were well enough to be referred was unchanged after steroids came into general use; 2. Younger patients (under 50 years) did not have a longer survival than older patients; 3. The size of the dose of irradiation did not affect survival over the range of doses employed; 4. The size of the treatment volume employed did not affect survival over the range of treatment volumes employed.

Brain Neoplasms↗
PubMed1982

Radiobiology of pions at TRIUMF.

Radiobiological studies at TRIUMF of the effects of pion beams have been carried out using cultured cells, mice and pigs. CHO cells in gel/medium were used for RBE determinations throughout the dose distributions. The RBE was shown to increase with depth in the stopping region, while the average RBE value decreased with increasing width of the stopping peak and also increased with increasing field size. The results suggest that the effects of peak width and field size will approximately cancel out when treatment volumes are changed, provided that all three dimensions are changed more or less proportionally. The peak center RBE values ranged from 1.2-1.3 for single doses. The oxygen enhancement ratio (OER) for pions was 2.2 compared to 2.8 for X rays. Split dose recovery was found to be somewhat reduced in the peak region. In vivo studies with mouse and pig skin have been done for 1 to 20 fractions. For mouse skin, pions showed an RBE of 1.5-1.6 for fraction numbers greater than 10. The RBE for pig skin was 1.4 for early reactions, but it may be higher for medium term reactions.

Animals↗
PubMed1982

Pions, Vancouver.

Clinical treatments at TRIUMF started in November, 1979. Ten patients with malignant subcutaneous nodules had 14 lesions treated with pions and 37 other nodules treated with 280 kV X rays. Three different fractionation regimens were used with X ray doses spanning the expected RBE range of pions. The RBE for pions for acute skin reaction for 10 fractions had a mean value about 1.5, while for 3 fractions it was 1.3 maximum. No dissociation of acute and late skin effects was seen with follow-up to 27 months after treatment. Phase 1-2 studies of Pion-Boost Therapy for patients with glioblastoma multiforme will begin in May, 1982. These will be followed in August with treatments of advanced pelvic malignancies using pions only. The existing beam line at TRIUMF will be upgraded and commitments have been given to go to higher beam currents. As a result, the dose rate should increase by a factor of at least two, allowing treatment of clinically relevant volumes in acceptable times by 1983-1984.

Brain Neoplasms↗
PubMed1982

Superfractionation: its rationale and anticipated benefits.

This manuscript discusses the biological bases of radiation therapy dose fractionation with emphasis on the theoretical implications of the quadratic cell survival equation (S = e-(alpha D + beta D2) ). In the development of the analysis, both the therapeutic ratio, defined as the log tumor cell survival divided by the log normal cell survival, and the therapeutic gain, the ratio of the therapeutic ratios for two different doses per treatment, are shown to be useful. From the analysis it follows that the use of small doses per treatment delivered at short intervals (superfractionation), will generally lead to improved local tumor control rates provided the total dose is increased sufficiently to maintain a constant level of normal tissue damage. Improvement may not be seen if the tumor response is dominated by oxygenated cells with a higher capacity to repair sublethal radiation injury than the host normal tissues.

Cell Cycle↗
PubMed1977

Preliminary results using superfractionation in the treatment of glioblastoma multiforme.

Preliminary results of a phase I--phase II trial of the use of superfractionation radiation treatment in the treatment of Glioblastoma Multiforme are presented with the rationale for this form of treatment. A comparison is made with an historic control group from the same institution, and a significant improvement in survival is noted in the experimental group over this control group.

Astrocytoma↗
PubMed1976

Changes in the proliferation rate of mouse epidermis after irradiat-on continuous labelling studies.

The proliferative response of mouse skin to damage caused by X-irradiation has been tested by giving repeated injections of tritiated thymidine and scoring the percentage of labelled cells in high resolution autoradiography. Four, nine and fourteen daily fractions of 300 rads of X-rays were used and labelling commenced 4 days after the last fraction. The epidermis of the upper surface and the sole of the foot were scored separately and were compared with the skin of unirradiated feet. In unirradiated skin the proliferation rate of the basal layer cells is more rapid on the sole than on the upper surface. The cell cycle times deduced from continuous labelling curves were 81 hr and 111 hr respectively and the growth fractions were 97% and85%. After irradiation with small daily doses the homeostatic response to cell killing was slow. More rapid proliferation occurred after nine fractions in the sole, but was not apparent in the skin of the upper surface until fourteen fractions had been given. After fourteen fractions the cell cycle time was about 24 hr on both surfaces and the growth fraction was about 90%. The initial labelling index after a single thymidine injection was a poor measure of proliferation rate. The delay in the time of onset of faster proliferation is similar, both qualitatively and quantitatively, to that measured previously from the additional dose increments needed if large doses were given at different times after the multifraction treatments (Denekamp, 1973).

Animals↗