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.
OBJECTIVE
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 (Tpot) of this tumor to the effective doubling time (Teff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times.


METHODS
The TCP was assessed 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 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 Tpot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to Teff.


RESULTS
The TCD50 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 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 Tpot (2.4 days) was longer than the calculated Teff in groups 2 and 3 (1.35 days).


CONCLUSIONS
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 clonogens. The pretreatment Tpot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen.
Allam
A
A
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Perez
L A
LA
Huang
P
P
Taghian
A
A
Azinovic
I
I
Freeman
J
J
Duffy
M
M
Efird
J
J
Suit
H D
HD
D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011879:Radiotherapy Dosage; D012509:Sarcoma / Q000473:pathology / Q000532:radiotherapy*; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014183:Transplantation, Heterologous