How valid is the assumption of equal effect per fraction?

• Published in: Radiotherapy and oncology Vol. 53; no. 3; pp. 227 - 231
• Main Authors: Rezvani, M, Ross, G, Morris, G M, Bywaters, A, Wilkinson, J H, Hopewell, J W
• Format: Journal Article
• Language: English
• Published: Ireland 01.12.1999
• Subjects: Animals; Cobalt Radioisotopes - administration & dosage; Cobalt Radioisotopes - therapeutic use; Disease Models, Animal; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Female; Foot - radiation effects; Foot Dermatoses - etiology; Incidence; Linear Models; Radiation Injuries, Experimental - etiology; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - therapeutic use; Radiotherapy Dosage; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Skin - radiation effects
• ISSN: 0167-8140
• DOI: 10.1016/S0167-8140(99)00148-6

The validity of the assumption of equal biological effect with dose per fraction in fractionated radiotherapy has been examined for the acute skin reaction in a rat foot model using a variable number of 2-Gy daily fractions followed by graded top-up doses. Mature female rats were used. Both hind feet of each rat were irradiated with a range of fractionated and top-up doses of 60Co gamma-rays. The dose-related incidence of moist desquamation was used as an end-point. Quantal data for the incidence of moist desquamation were analysed using probit analysis and ED50 (+/-SE) values were obtained. The results were also compared with predicted values obtained from the application LQ-model. After a single 2-Gy fraction followed by top-up doses 24 h later, the dose effect curve for the top-up doses used was shifted to lower doses as expected and the ED50 for moist desquamation of 19.78 +/- 0.13 Gy was 1.16 Gy less than the ED50 of 20.94 +/- 0.15 Gy for large single dose exposure alone. This implied that only approximately 58% of the initial 2-Gy fraction was effective, and the rest was repaired within a 24-h interval between the 2 Gy and top-up doses. However, after two or three 2-Gy daily fractions the dose effect curves for the subsequent top-up doses moved to the higher doses again and the ED50 for top-up dose increased to 20.33 +/- 0.21 and 20.75 +/- 0.11 Gy, respectively. A further increase in the number of 2-Gy daily fractions shifted the dose effect curves for the top-up doses to lower doses and ED50 values for the top-up doses decreased progressively. The findings were not in keeping with values predicted based on the assumption of equal effect per fraction and could not be explained by the use of a single alpha/beta ratio in the LQ-model.