Impact of increased cell loss on the repopulation rate during fractionated irradiation in human FaDu squamous cell carcinoma growing in nude mice.
OBJECTIVE
To determine the impact of increased necrotic cell loss on the repopulation rate of clonogenic cells during fractionated irradiation in human FaDu squamous cell carcinoma in nude mice.


METHODS
FaDu tumours were transplanted into pre-irradiated subcutaneous tissues. This manoeuvre has previously been shown to result in a clear-cut tumour bed effect, i.e. tumours grow at a slower rate compared with control tumours. This tumour bed effect was caused by an increased necrotic cell loss with a constant cell production rate. After increasing numbers of 3-Gy fractions (time intervals 24 or 48 h), graded top-up doses were given to determine the dose required to control 50% of the tumours (TCD50). All irradiations were given under clamp hypoxia.


RESULTS
With increasing numbers of daily fractions, the top-up TCD50 decreased from 37.9 Gy (95% CI: 31; 45) after single dose irradiation to 14.1 Gy (8; 20) after irradiation with 15 fractions in 15 days. Irradiation with 18 daily 3-Gy fractions controlled more than 50% of the tumours without a top-up dose. After irradiation with six fractions every second day, the top-up TCD50 decreased to 26.9 Gy (22; 32). No further decrease of the TCD50 was observed after 12 and 18 irradiations every second day. Assuming a constant increase of TCD50 with time, the calculated doubling time of the clonogenic tumour cells (Tclon) was 7.8 days (4.4; 11.3). The Tclon calculated for FaDu tumours growing in pre-irradiated tissues was significantly longer (p=0.0004) than the Tclon of 5.1 days (3.7; 6.5) determined under the same assumptions in a previous study for FaDu tumours growing in normal subcutaneous tissues.


CONCLUSIONS
Increased necrotic cell loss by pre-irradiation of the tumour bed resulted in longer clonogen doubling times during fractionated radiotherapy of human FaDu squamous cell carcinoma. This implies that a decreased necrotic cell loss might be the link between reoxygenation and repopulation demonstrated previously in the same tumour model.
Hessel
F
F
Clinic of Radiation Oncology, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany.
Petersen
C
C
Zips
D
D
Krause
M
M
Pfitzmann
D
D
Thames
H D
HD
Baumann
M
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy*; D002455:Cell Division / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000528:radiation effects; D014183:Transplantation, Heterologous