The effect of fraction time in intensity modulated radiotherapy: theoretical and experimental evaluation of an optimisation problem.

BACKGROUND AND PURPOSE In intensity modulated radiotherapy (IMRT), the complexity and the number of treatment fields have expanded. This may imply that the delivery time for each fraction becomes prolonged. In a number of IMRT techniques used in the clinic, the delivery time per fraction is usually 10-15 min, sometimes more than 15 min. In studies on human skin, prolonged delivery time is shown to cause significant reduction of radiation effects compared with acute irradiation. In this paper the effect of changes in fraction delivery time was studied by in vitro irradiation of mammalian cells. MATERIAL AND METHODS Chinese hamster fibroblasts (V79-379-A) were used for simulating clinical situations. Most experiments were performed with 2Gy/fraction with 4-h intervals in 40-60 replicates. Each fraction was divided into different subfractions, simulating the delivery of a complicated treatment. The effect of changing the delivery time for each fraction was studied. Parameters for the cell survival curve and repair kinetics were determined experimentally. The same methods were also used for large fraction sizes (8Gy). The validity of the most widely used models in the literature, all derived from linear-quadratic formalism, were tested against the experimental results. RESULTS The effect of prolonging the fraction time for 2-Gy fractions was underestimated by the biological models. The experiments showed that 10-min prolonged delivery time gave a ratio between surviving fractions at 2Gy (S-ratio) of 1.054 with a 95% confidence interval (CI) 1.030-1.080, while the models predicted 1.007 and 1.009. Extending the fraction time to 20 min gave an S-ratio of 1.063 with CI of 1.045-1.080, while the models predicted 1.012 and 1.014. For 8-Gy fractions, there was a good agreement between predications and experimental results. The ratio between surviving fractions at 8Gy is 1.370 with CI of 1.300-1.440, while the models predicated 1.37 and 1.35. CONCLUSIONS The effect of prolonging fraction time at conventional dose/fraction is underestimated by biological models. Prolonging the fraction time will spare tissues with a fast DNA repair. There is a risk for sparing tumours. This should be considered when IMRT technique is implemented in the clinic.

[1]  A. Wambersie,et al.  Application of the LQ model to the interpretation of absorbed dose distribution in the daily practice of radiotherapy. , 1991, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[2]  PHYSICAL CONSIDERATIONS IN THE USE OF INTENSITY MODULATED RADIOTHERAPY TO PRODUCE THREEDIMENSIONAL CONFORMAL DOSE DISTRIBUTIONS , 2000 .

[3]  M. F. Eschwège.  Conformal Radiotherapy and Intensity-modulated Radiotherapy: Clinical Data , 2000, Acta oncologica.

[4]  H D Thames,et al.  An 'incomplete-repair' model for survival after fractionated and continuous irradiations. , 1985, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[5]  B. Zackrisson,et al.  Relative biological effectiveness of high-energy photons (up to 50 MV) and electrons (50 MeV). , 1991, Radiation research.

[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]  H. Thames,et al.  A parametric method for estimation of dose-modifying factors: low-dose extrapolation limit. , 1977, Radiation research.

[8]  G. Steel,et al.  Recovery from radiation damage in human squamous carcinoma of the cervix. , 1989, International journal of radiation biology.

[9]  Mortimer M. Elkind,et al.  The radiobiology of cultured mammalian cells , 1967 .

[10]  B. Marples,et al.  The response of Chinese hamster V79 cells to low radiation doses: evidence of enhanced sensitivity of the whole cell population. , 1993, Radiation research.

[11]  I. Turesson,et al.  The influence of irradiation time per treatment session on acute and late skin reactions: a study on human skin. , 1984, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[12]  T. Cullip,et al.  Intensity modulation delivery techniques: "step & shoot" MLC auto-sequence versus the use of a modulator. , 2000, Medical physics.

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

[14]  A. Ruifrok,et al.  Comparison of continuous and pulsed low dose rate brachytherapy: biological equivalence in vivo. , 1994, International journal of radiation oncology, biology, physics.

[15]  E. Dikomey,et al.  Three classes of DNA strand breaks induced by X-irradiation and internal β-rays , 1986 .

[16]  I. Turesson.  Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation. , 1990, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[17]  R Mohan,et al.  Conformal radiation treatment of prostate cancer using inversely-planned intensity-modulated photon beams produced with dynamic multileaf collimation. , 1996, International journal of radiation oncology, biology, physics.

[18]  B. Zackrisson,et al.  Relative biological effectiveness and oxygen enhancement ratio of 50 MV X-rays. , 1989, Acta oncologica.

[19]  B. Zackrisson,et al.  Radiobiological cell survival models. A methodological overview. , 1992, Acta oncologica.

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