The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice

Abstract

Purpose : To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (T pot) of this tumor to the effective doubling time (T eff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. Methods and Materials : The TCP was assessed using the TCD 50 value (the 50% tumor control dose) as an end pont. A total of 240 male nude mice, 7–8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7–8 mm. The mean interfraction intervals were from 8–24 h. The T pot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry adn was compared to T eff. Results : The TCD 50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD 50 values was significant ( p < 0.05) between groups 1 and 2 (30 fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days). The loss in TCP due to the prolongation of teh overall treatment time for 10 days to 30 days was found to be 1.35–1.4 Gy/day. The pretreatment T pot (2.4 days) was longer than the calculated T eff in groups 2 and 3 (1.35 days). Conclusion : Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clongens. The pretreatment T pot of this tumor model does not reflect the actual dougling of the clonogens in a protracted regimen.