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

The effects of fractionated doses of fast neutrons (42 MeVd----Be) on the radiation response of the pig kidney have been assessed and compared with those observed after X irradiation. Following X irradiation there was a marked increase in the total dose at which renal function was preserved with decreasing fraction size. The rate of this increase was dependent on the overall treatment time; for fractionated irradiation given over 18 or 39 days the exponents related to fraction number, N, were 0.36 +/- 0.03 and 0.48 +/- 0.003, respectively. In contrast, there was no significant change in the iso-effect dose for renal injury following fractionated irradiation with fast neutrons where there was also little effect of varying the overall treatment time. Analysing these data by means of the linear-quadratic (LQ) model, using both an Fe-plot and the Tucker test, gave alpha/beta ratios of 2.42 +/- 0.06 Gy and 2.99 +/- 0.16 Gy, respectively, for X-ray doses given in 18 days. For fractionated doses of X rays given in 39 days the alpha/beta ratios were 0.40 +/- 0.01 Gy and 0.47 +/- 0.02 Gy, respectively. The alpha/beta ratios for renal tissue following fast neutron irradiation obtained by the two methods were also similar, i.e. 15.00 +/- 0.60 Gy and 15.72 +/- 3.76 Gy, respectively. The pronounced fractionation effect seen with X irradiation, particularly for doses administered over 39 days as opposed to 18 days, coupled with the absence of any such effect with fast neutrons, resulted in a marked increase in relative biological effectiveness (RBE) with decreasing X-ray dose/fraction. The slopes of the resulting regression lines were -0.73 +/- 0.05 and -0.33 +/- 0.02, respectively. The lack of dose sparing associated with fractionation, or variation of the overall treatment time for fast neutron irradiation, suggests that doses administered to tumours adjacent to the kidney can be given as a few relatively large dose/fractions in a short overall treatment time without an increased risk of complications related to renal tissue. This may be of therapeutic advantage in the treatment of rapidly proliferating tumours where dose may be wasted using more conventional protracted fractionated irradiation schedules.

[1]  J. Hopewell,et al.  Radiation tolerance of the pig kidney: a model for determining overall time and fraction factors for preserving renal function. , 1975, International journal of radiation oncology, biology, physics.

[2]  D. Bonnett,et al.  The Clatterbridge high-energy neutron therapy facility: specification and performance. , 1988, The British journal of radiology.

[3]  The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. II. Late effects on cutaneous and subcutaneous tissues. , 1990, The British journal of radiology.

[4]  Single dose fast neutron RBE for pulmonary and esophageal damage in mice. , 1976, Radiology.

[5]  H. Rossi.  Relative biological effectiveness , 1989 .

[6]  M. Williams,et al.  Radiation induced renal damage in mice: influence of fraction size. , 1984, International journal of radiation oncology, biology, physics.

[7]  M. Williams,et al.  Radiation-induced renal damage: the effects of hyperfractionation. , 1984, Radiation research.

[8]  N. Hubbard,et al.  The Large White female pig in research related to cancer treatment: general husbandry and anaesthesia. , 1990 .

[9]  E. Hall,et al.  RBE as a function of neutron energy , 1975 .

[10]  S. Lehnert,et al.  The use of CT densitometry in the assessment of radiation-induced damage to the rat lung: a comparison with other endpoints. , 1989, International journal of radiation oncology, biology, physics.

[11]  D. K. Bewley,et al.  First results of a randomized clinical trial of fast neutrons compared with X or gamma rays in treatment of advanced tumours of the head and neck. Report to the Medical Research Council. , 1975, British medical journal.

[12]  J. Hopewell,et al.  Radiation – Related Renal Damage , 1987 .

[13]  J. Hopewell,et al.  The predictive value of the NSD system for renal tolerance to fractionated x-irradiation in the pig. , 1974, British Journal of Radiology.

[14]  A. J. van der Kogel,et al.  Lack of evidence for increased tolerance of rat spinal cord with decreasing fraction doses below 2 Gy. , 1985, International journal of radiation oncology, biology, physics.

[15]  J. Hopewell,et al.  The validity of different methods of analysis of 133Xe washout curves for the determination of lung function. , 1986, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[16]  G. Read,et al.  A randomised comparison of photons and 15 MeV neutrons for the treatment of carcinoma of the bladder. , 1985, The British journal of radiology.

[17]  M. Joiner,et al.  Renal damage in the mouse: the effect of d(4)-Be neutrons. , 1987, Radiation research.

[18]  S. B. Field,et al.  A comparison for use in radiotherapy of neutron beams generated with 16 and 42 MeV deuterons on beryllium. , 1976, The British journal of radiology.

[19]  E. W. Bradley,et al.  A comparison of neutron RBE values for normal canine lung by densitometry, pulmonary function and radionuclide studies. , 1981, International journal of radiation oncology, biology, physics.

[20]  H. Bartelink,et al.  Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose. , 1987, International journal of radiation oncology, biology, physics.

[21]  H. Withers,et al.  Relative biological effectiveness (RBE) of 50 MV (Be) neutrons for acute and late skin injury. , 1978, International journal of radiation oncology, biology, physics.

[22]  S. Tucker.  Tests for the fit of the linear-quadratic model to radiation isoeffect data. , 1984, International journal of radiation oncology, biology, physics.

[23]  E. Hall,et al.  RBE as a function of neutron energy. I. Experimental observations. , 1975, Radiation research.

[24]  J. Hopewell,et al.  The response of the pig lung to fractionated doses of X rays. , 1990, The British journal of radiology.

[25]  D. Goodhead,et al.  High energy fast neutrons from the Harwell variable energy cyclotron. I. Physical characteristics. , 1977, AJR. American journal of roentgenology.

[26]  G. Remuzzi,et al.  Metabolism of arachidonic acid in isolated glomeruli from pig kidney. , 1988, Biochimica et biophysica acta.

[27]  S. B. Field,et al.  Damage to mouse lung with neutrons and x-rays. , 1974, European journal of cancer.

[28]  J. Fowler,et al.  Repair in mouse lung of multifraction X rays and neutrons: extension to 40 fractions. , 1985, The British journal of radiology.

[29]  E. Hall,et al.  RBE as a function of neutron energy. II. Statistical analysis. , 1976, Radiation Research.

[30]  J. Fowler,et al.  Repair in mouse lung for up to 20 fractions of X rays or neutrons. , 1985, The British journal of radiology.

[31]  J. Hopewell,et al.  Kinetics of recovery from sublethal radiation damage , 1989 .

[32]  H. Withers,et al.  Biological bases for high RBE values for late effects of neutron irradiation. , 1982, International journal of radiation oncology, biology, physics.

[33]  J. Hopewell,et al.  Effects of single doses of X-rays on renal function in the pig after the irradiation of both kidneys. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[34]  E. W. Bradley,et al.  Effects of fast neutrons on rabbits-II. Comparison of pathologic effects of fractionated neutron and photon exposures of the lung and spinal cord. , 1979, International journal of radiation oncology, biology, physics.

[35]  W. J. Hooper.  THE DEPOSITION OF DUST ON WALLS , 1931 .

[36]  S. B. Field,et al.  The response of mouse skin to irradiation with neutrons from the 62 MV cyclotron at Clatterbridge, U.K. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[37]  F. Stewart,et al.  Does incomplete repair explain the apparent failure of the basic LQ model to predict spinal cord and kidney responses to low doses per fraction? , 1988, International journal of radiation biology.

[38]  E. van Rongen,et al.  Fractionation effects and repair kinetics in rat kidney. , 1990, International journal of radiation oncology, biology, physics.

[39]  J. Hopewell,et al.  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. , 1988, The British journal of radiology.

[40]  J. Hopewell,et al.  Studies of dose-fractionation on early and late responses in pig skin: a reappraisal of the importance of the overall treatment time and its effects on radiosensitization and incomplete repair. , 1991, International journal of radiation oncology, biology, physics.

[41]  S. Hornsey.  RBE for lung and cord. , 1982, International journal of radiation oncology, biology, physics.

[42]  T. Herrmann,et al.  Fractionated lung irradiation in young pigs with 6.2 MeV neutrons and cobalt-60. , 1986, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[43]  The uptake of rubidium-86 in mouse kidneys irradiated with fractionated doses of x rays. , 1975, Radiation research.

[44]  J. Hopewell,et al.  Effects of single doses of gamma-radiation on pig lung. , 1989, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[45]  M. Joiner.  A comparison of the effects of p(62)-Be and d(16)-Be neutrons in the mouse kidney. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[46]  S. B. Field.  An historical survey of radiobiology and radiotherapy with fast neutrons. , 1976, Current topics in radiation research quarterly.

[47]  D. K. Bewley,et al.  Fast Neutrons in the Treatment of Cancer , 1979 .

[48]  S. B. Field,et al.  Damage to mouse lung with fractionated neutrons and x rays. , 1975, Radiology.

[49]  H. Withers,et al.  Response of mouse jejunum to multifraction radiation. , 1975, International journal of radiation oncology, biology, physics.

[50]  M. Robbins,et al.  Techniques for the quantitative measurement of individual kidney function in the pig. , 1984, The International journal of applied radiation and isotopes.