The assessment of RBE effects using the concept of biologically effective dose.

PURPOSE To modify existing linear-quadratic (LQ) equations in order to take account of relative biological effectiveness (RBE) using the concept of biologically effective dose (BED). METHODS AND MATERIALS Clinically useful forms of the LQ model have been modified to incorporate RBE effects in such a way as to allow comparison between high- and low-LET (linear energy transfer) radiations in terms of similar biological dose units. The new parameter in the formulation is RBEM, the intrinsic (or maximum) RBE at zero dose. The principal assumption (following Kellerer and Rossi; ref. 1) is that high-LET radiation modifies the alpha-coefficient of damage while leaving the beta-coefficient unaltered. RESULTS The equations allow a quantitative estimation of how the apparent RBE will change with changes in dose/fraction or dose-rate and of how the magnitude and rate of change is governed by the low-LET alpha/beta ratio of the irradiated tissue. The modifications are applicable to all types of radiotherapy (fractionated, continuous low dose-rate, therapy with decaying sources, etc.). In cases where the normal tissue RBEM is greater than that for the tumor, the revised formulation helps explain why there will be situations where therapeutic index will be adversely affected by use of high-LET radiation. Such clinical advantages as have been observed are more likely to result from favorable geometrical sparing of critical normal tissues and/or the fact that slowly growing tumors may have alpha/beta values more typical of late-responding normal tissues. CONCLUSIONS The incorporation of RBE into existing LQ methodology allows quantitative assessment of clinical applications of high-LET radiations via an examination of the associated BEDs. On the basis of such assessments high-LET radiations are shown to confer few advantages.

[1]  A. Wambersie,et al.  Which RBE for iodine 125 in clinical applications? , 1987, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[2]  R. Hawkins A statistical theory of cell killing by radiation of varying linear energy transfer. , 1994, Radiation research.

[3]  J. Battista,et al.  The relative biological effectiveness of ytterbium-169 for low dose rate irradiation of cultured mammalian cells. , 1993, International journal of radiation oncology, biology, physics.

[4]  J. Fowler,et al.  Early and late injuries in mouse rectum after fractionated X-ray and neutron irradiation. , 1993, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[5]  M. Zaider,et al.  The relative biological effectiveness of photon radiation from encapsulated iodine-125, assessed in cells of human origin: I. Normal diploid fibroblasts. , 1990, International journal of radiation oncology, biology, physics.

[6]  A. Kellerer,et al.  A Generalized Formulation of Dual Radiation Action1 , 1978 .

[7]  G. Barendsen,et al.  Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. , 1982, International journal of radiation oncology, biology, physics.

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

[9]  C C Ling,et al.  The relative biological effectiveness of I-125 and Pd-103. , 1995, International journal of radiation oncology, biology, physics.

[10]  R G Dale,et al.  The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. , 1985, The British journal of radiology.

[11]  C. Ling,et al.  Conformal radiation treatment: a critical appraisal. , 1995, European journal of cancer.

[12]  B. Stenerlöw,et al.  Irregular variations in radiation sensitivity when the linear energy transfer is increased. , 1995, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[13]  P. Deschavanne,et al.  In vitro radiosensitivity of six human cell lines. II. Relation to the RBE of 50-MeV neutrons. , 1982, Radiation research.

[14]  E. Hall,et al.  Low Dose‐Rate Effects of Cesium‐137 and Iodine‐125 on Cell Survival, Cell Progression, and Chromosomal Alterations , 1986, American Journal of Clinical Oncology.

[15]  R. Dale,et al.  Effect of tumour shrinkage on the biological effectiveness of permanent brachytherapy implants. , 1994, The British journal of radiology.

[16]  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.

[17]  P Wootton,et al.  Impact of a multileaf collimator on treatment morbidity in localized carcinoma of the prostate. , 1994, International journal of radiation oncology, biology, physics.

[18]  The effect of tumour shrinkage on biologically effective dose, and possible implications for fractionated high dose rate brachytherapy , 1994 .

[19]  J. Denekamp,et al.  The interaction between X-rays and 3 MeV neutrons in the skin of the mouse foot. , 1984, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[20]  E. Hall,et al.  Studies with encapsulated 125I sources. II. Determination of the relative biological effectiveness using cultured mammalian cells. , 1981, International journal of radiation oncology, biology, physics.

[21]  H. Warenius,et al.  The inherent cellular sensitivity to 62.5 MeV(p----Be+) neutrons of human cells differing in photon sensitivity. , 1992, International journal of radiation biology.

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

[23]  K. Trott,et al.  Possible dose rate dependence of recovery kinetics as deduced from a preliminary analysis of the effects of fractionated irradiations at varying dose rates. , 1988, The British journal of radiology.

[24]  J. J. Broerse,et al.  Relative biological effectiveness of fast neutrons for effects on normal tissues. , 1973, Current topics in radiation research quarterly.

[25]  R Goodall,et al.  The 62 MeV proton beam for the treatment of ocular melanoma at Clatterbridge. , 1993, The British journal of radiology.

[26]  A Wambersie,et al.  Review of the clinical results of fast neutron therapy. , 1990, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[27]  S. Tucker,et al.  Isoeffect models and fractionated radiation therapy. , 1987, International journal of radiation oncology, biology, physics.

[28]  R. Dale,et al.  Derivation of the optimum dose per fraction from the linear quadratic model. , 1995, The British journal of radiology.