Viability of the EUD and TCP concepts as reliable dose indicators.

The concept of equivalent uniform dose (EUD) was introduced to provide a method of reporting radiotherapy dose distributions which takes account of the nonlinearity of tissue dose-response, whilst not attempting to make predictions of absolute outcome. The purpose of this investigation was to determine the level of sensitivity of EUD to model parameters for significant variations in dose distribution and consequently the reliability of the factor as a dose-indicator, and to compare EUD with the more familiar index, tumour control probability (TCP). EUD and TCP, derived from the linear-quadratic formalism, were investigated for a test tissue being irradiated non-uniformly. Variations in the parameters of the model (tissue cell characteristics, dose heterogeneity, fractionation parameters) indicated the sensitivity of EUD and TCP to them. For time independent factors--cell density, cell radiosensitivity, radiosensitivity heterogeneity (population averaged) and ratio alpha/beta--EUD was found to vary insignificantly in comparison with TCP, though this is a function of the actual form of the dose distribution under consideration. For fractionated treatments where the mean dose per fraction is varying (due to dosimetric/positioning errors for example), both EUD and TCP showed little variation with the degree of dose non-uniformity. For other time dependent factors, fractionation rate and cell repopulation times, TCP again showed significant variation relative to EUD. The relative insensitivity of EUD implies that this index will be useful for dose evaluation when parameters are not known with accuracy, for the intercomparison of dose control studies and as a radiobiologically based optimization objective. However, given confidence in model parameters, the sensitivity of TCP would make it a more reliable tool for indicating potentially successful and unsuccessful irradiation strategies. It is suggested that both parameters be used in conjunction, with EUD and TCP results viewed with an appreciation of the characteristics of each model.

[1]  P. Hoban,et al.  Some characteristics of tumour control probability for heterogeneous tumours. , 1996, Physics in medicine and biology.

[2]  J. Fowler The linear-quadratic formula and progress in fractionated radiotherapy. , 1989, The British journal of radiology.

[3]  A. Brahme,et al.  Optimal dose distribution for eradication of heterogeneous tumours. , 1987, Acta oncologica.

[4]  P Aaltonen,et al.  Specification of dose delivery in radiation therapy , 1997 .

[5]  S Webb,et al.  A model for calculating tumour control probability in radiotherapy including the effects of inhomogeneous distributions of dose and clonogenic cell density. , 1993, Physics in medicine and biology.

[6]  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.

[7]  Comment on "Reporting and analyzing dose distributions: a concept of equivalent uniform dose" [Med. Phys. 24, 103-109 (1997)]. , 1997, Medical physics.

[8]  R. Pearcey,et al.  Intratumoral heterogeneity as a confounding factor in clonogenic assays for tumour radioresponsiveness. , 1996, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  B. Paliwal,et al.  Quality Assessment and Improvement of Dose Response Models: Some Effects of Study Weaknesses on Study Findings "C'est Magnifique?" , 1993 .

[10]  P Aaltonen,et al.  Specification of dose delivery in radiation therapy. Recommendation by the Nordic Association of Clinical Physics (NACP). , 1997, Acta oncologica.

[11]  P Okunieff,et al.  Clinical implications of heterogeneity of tumor response to radiation therapy. , 1992, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[12]  J. Fowler The volume effect in radiotherapy. , 1993 .

[13]  H. Thames,et al.  The effect of patient-to-patient variability on the accuracy of predictive assays of tumor response to radiotherapy: a theoretical evaluation. , 1989, International journal of radiation oncology, biology, physics.

[14]  T E Schultheiss,et al.  Inter-tumor heterogeneity and radiation dose-control curves. , 1987, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  A. Brahme,et al.  The need for accurate target and dose specifications in conventional and conformal radiation therapy--an introduction. , 1997, Acta oncologica.

[16]  A Brahme,et al.  Tumour and normal tissue responses to fractionated non-uniform dose delivery. , 1992, International journal of radiation biology.

[17]  Andrzej Niemierko Response to “Comment on ‘Reporting and analyzing dose distributions:\sA concept of equivalent uniform dose’ ” [Med Phys. 24, 1323–1324 (1997)] , 1997 .

[18]  A. Niemierko Reporting and analyzing dose distributions: a concept of equivalent uniform dose. , 1997, Medical physics.

[19]  S M Bentzen,et al.  Quantitative clinical radiobiology. , 1993, Acta oncologica.

[20]  A Brahme,et al.  Dosimetric precision requirements in radiation therapy. , 1984, Acta radiologica. Oncology.