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

Purpose: To study the impact of the overall treatment time of fraction ated irradiation on the tumor control probability (TCP) of a human sof t 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 schedule s of irradiation using the same total number of fractions with differe nt overall treatment times. Methods and Materials: The TCP was assesse d using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experi mental groups that received the same total number of fractions (30 fra ctions) with different overall treatment times. In group 1, the animal s 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 and was comp ared to T-eff. Results: The TCD50 values of the three different treatm ent schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 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 the overall treatment time from 10 days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment T-pot (2.4 days) was lo nger than the calculated T-eff in groups 2 and 3 (1.35 days). Conclusi on: Our data show a significant loss in TCP with prolongation of the o verall treatment time. This is most probably due to an accelerated rep opulation of tumor clonogens. The pretreatment T-pot of this tumor mod el does not reflect the actual doubling of the clonogens in a protract ed regimen.