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Dose fractionation, dose rate and iso-effect relationships for normal tissue responses

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Abstract

An analysis is,,presented of responses of a variety of normal tissues in animals to fractionated irradiations. It is shown that the influence of fractionation can be described on the basis of a simple formula relating the effectiveness for induction of cellular effects to the dose per fraction: F(D) = 1D + a2D2. The ratio a1a2 is derived as an essential parameter for, the description of fractionation effects. It is concluded that the values of a1a2 for responses of various tissues range widely from 2 to 10 Gy. On the basis of the review of radiobiological data, a formalism is developed for the analysis and prediction of iso-effect relations for tissue tolerance, which can be used as an alternative to the nominal standard dose (NSD) formula of Ellis and its derived equations. An essential characteristic of the formalism is that three groups of tissue responses are distinguished which can be described with respect to fractionation effects by average values of ala2 = 10; 5 and 2.5 Gy, respectively. These groups comprise a l: a.o. skin and intestine; 2: connective tissue; 3:a.o. lung and vascular system. Dose rate effects can be described by a similar formalism. For the calculation of equivalent total doses to be applied in clinical treatments, a concept denoted Extrapolated Tolerance Dose (ETD) of Extrapolated Response Dose (ERD) is introduced. ETD is the tolerance dose for an infinite number of very small fractions. This concept is shown to be useful for the summation of different fractionated schedules and of low dose rate treatments. A number of examples is presented illustrating similarities and differences in comparison with calculations based on the NSD formula. An important feature of the described formalism is that it is directly based on radiobiological insights and it provides a more logical concept to account for the diversity of tissue responses than the assumption of different exponents of N and T in the NSD formula.

References (74)

  • K. Masuda et al.

    Late effect in mouse skin following single and multifractionated irradiation

    Int. J. Radial. Oncol. Biol. Phys.

    (1980)
  • H.R. Withers et al.

    Response of mouse jejunum to multifraction radiation

    Int. J. Radiat. Oncol. Biol. Phys.

    (1975)
  • H.R. Withers et al.

    Effect of dose fractionation on late and early skin responses to gamma rays and neutrons

    Int. J. Radiat. Oncol. Biol. Phys.

    (1977)
  • G.W. Barendsen

    Fose-survival curves of human cells in tissue culture irradiated with alpha-, beta-, 20 kV X- and 200 kV X-radiation

    Nature

    (1962)
  • G.W. Barendsen

    Effects of single and repeated low doses of ionizing radiations on the proliferative capacity of human cells in culture

  • G.W. Barendsen

    Responses of cultured cells, tumours and normal tissues to radiations of different linear energy transfer

  • G.W. Barendsen

    Quantitative biophysical aspects of responses of tumours and normal tissues to ionizing radiations

    Curr. Top. Rad. Res. Quart.

    (1973)
  • G.W. Barendsen

    Characteristics of cell survival curves for different radiations in relation to iso-effect curves for fractionated treatments of a rat rhabdomyosarcoma

  • G.W. Barendsen

    The effectiveness of small doses of ionizing radiations for the induction of cell reproductive death, chromosomal changes and malignant transformation

  • G.W. Barendsen

    Fundamental aspects of cancer induction in relation to the effectiveness of small doses of radiation.

  • G.W. Barendsen

    Influence of radiation quality on the effectiveness of small doses for induction of reproductive death and chromosome aberrations in mammalian cells

    Int. J. Radiat. Biol.

    (1979)
  • G.W. Barendsen

    Variations in radiation responses among experimental tumors

  • G.W. Barendsen

    Intrinsic radiosensitivity of tumour cells

  • T.D. Bates et al.

    Dangers of the clinical use of the NSD formula for small fraction numbers

    Br. J. Radiol.

    (1975)
  • R.J. Berry et al.

    Skin tolerance to fractionated X-irradiation in the pig-how good a predictor is the NSD formula?

    Br. J. Radiol.

    (1974)
  • J.M. Brown

    The shape of the dose-response curve for radiation carcinogenesis. Extrapolation to low doses

    Rad. Res.

    (1977)
  • W.L. Caldwell

    Time-dose factors in fatal post-irradiation nephritis

  • K.H. Chadwick et al.

    A molecular theory of cell survival

    Phys. Med. Biol.

    (1973)
  • L. Cohen et al.

    Estimation of biological dosage factors in clinical radiotherapy

    Br. J. Cancer

    (1951)
  • R. Cox et al.

    Inactivation and mutation of cultured mammalian cells by alluminium characteristic ultrasoft X-rays. 11. Dose-response of Chinese hamster and human diploid cells to aluminium X-rays and radiation of different LET

    Int. J. Rad. Biol.

    (1977)
  • J. Denekamp

    Changes in the rate of repopulation during multifraction irradiation of mouse skin

    Br. J. Radiol.

    (1973)
  • S. Dische et al.

    Radiation myelopathy in patients treated for carcinoma of bronchus using a six fraction regime of radiotherapy

    Br. J. Radiol.

    (1981)
  • B.G. Douglas et al.

    Fractionation schedules and quadratic dose-effect relationship

    Br. J. Radiol.

    (1975)
  • B.G. Douglas et al.

    The effect of multiple small doses of X rays on skin reactions in the mouse and a basic interpretation

    Rad. Res.

    (1976)
  • J. Dutreix et al.

    Clinical radiobiology of low dose-rate radiotherapy

    Br. J. Radiol.

    (1975)
  • M.M. Elkind

    A summary and review of the conference. In Cell Survival After Low Doses of Radiation: Theoretical and Clinical Implications

  • M.M. Elkind et al.

    Radiation response of mammalian cells grown in culture. I. Repair of X-ray damage in surviving Chinese hamster cells

    Rad. Res.

    (1960)
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