You need JavaScript to view this

The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (T{sub pot})

Abstract

Purpose: Repopulation during fractionated radiotherapy has been postulated to result in a significant loss in local control in rapidly proliferating tumors. Clinical data suggest that accelerated fractionation schedules can overcome the influence of repopulation by limiting the overall treatment time. Unfortunately, accelerated therapy frequently leads to increased acute reactions, which may become dose limiting. An alternative to accelerated fractionation would be to decrease the rate of repopulation during therapy. To test the potential efficacy of this alternative, we examined the effect of reducing tumor proliferation rate on the response of MCF-7 human breast carcinoma xenografts treated with a short vs. a long course of fractionated therapy. To reduce the proliferation rate, we deprived nude mice transplanted with MCF-7 xenografts of the growth-stimulating hormone estradiol (E{sub 2}). We have previously reported that E{sub 2} deprivation increases the potential doubling time (T{sub pot}) for MCF-7 xenografts from a mean of 2.6 days to 5.3 days (p < 0.001). Methods and Materials: E{sub 2}-stimulated and E{sub 2}-deprived MCF-7 breast carcinoma xenografts were clamped hypoxically and irradiated with four fractions of 5 Gy each, using either a short (3-day) or long (9-day) treatment course. E{sub 2} stimulation was restored in all animals at the  More>>
Publication Date:
Feb 15, 1995
Product Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 31; Journal Issue: 4; Other Information: PII: 0360301694005400; Copyright (c) 1995 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); PBD: 15 Feb 1995
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; CELL PROLIFERATION; ESTRADIOL; FRACTIONATED IRRADIATION; GRAFTS; MAMMARY GLANDS; TUMOR CELLS
OSTI ID:
20391022
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0360-3016; IOBPD3; TRN: US03R1472055967
Submitting Site:
INIS
Size:
page(s) 833-840
Announcement Date:
Nov 20, 2003

Citation Formats

Sarkaria, Jann N, Fowler, John F, Lindstrom, Mary J, Jordan, V Craig, and Mulcahy, R Timothy. The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (T{sub pot}). United States: N. p., 1995. Web. doi:10.1016/0360-3016(94)00540-0.
Sarkaria, Jann N, Fowler, John F, Lindstrom, Mary J, Jordan, V Craig, & Mulcahy, R Timothy. The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (T{sub pot}). United States. doi:10.1016/0360-3016(94)00540-0.
Sarkaria, Jann N, Fowler, John F, Lindstrom, Mary J, Jordan, V Craig, and Mulcahy, R Timothy. 1995. "The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (T{sub pot})." United States. doi:10.1016/0360-3016(94)00540-0. https://www.osti.gov/servlets/purl/10.1016/0360-3016(94)00540-0.
@misc{etde_20391022,
title = {The decreased influence of overall treatment time on the response of human breast tumor xenografts following prolongation of the potential doubling time (T{sub pot})}
author = {Sarkaria, Jann N, Fowler, John F, Lindstrom, Mary J, Jordan, V Craig, and Mulcahy, R Timothy}
abstractNote = {Purpose: Repopulation during fractionated radiotherapy has been postulated to result in a significant loss in local control in rapidly proliferating tumors. Clinical data suggest that accelerated fractionation schedules can overcome the influence of repopulation by limiting the overall treatment time. Unfortunately, accelerated therapy frequently leads to increased acute reactions, which may become dose limiting. An alternative to accelerated fractionation would be to decrease the rate of repopulation during therapy. To test the potential efficacy of this alternative, we examined the effect of reducing tumor proliferation rate on the response of MCF-7 human breast carcinoma xenografts treated with a short vs. a long course of fractionated therapy. To reduce the proliferation rate, we deprived nude mice transplanted with MCF-7 xenografts of the growth-stimulating hormone estradiol (E{sub 2}). We have previously reported that E{sub 2} deprivation increases the potential doubling time (T{sub pot}) for MCF-7 xenografts from a mean of 2.6 days to 5.3 days (p < 0.001). Methods and Materials: E{sub 2}-stimulated and E{sub 2}-deprived MCF-7 breast carcinoma xenografts were clamped hypoxically and irradiated with four fractions of 5 Gy each, using either a short (3-day) or long (9-day) treatment course. E{sub 2} stimulation was restored in all animals at the completion of irradiation. Radiation response was determined by regrowth time and regrowth delay of the irradiated tumors as compared to unirradiated controls. Results: Prolongation of therapy in rapidly proliferating, E{sub 2}-stimulated tumors (T{sub pot} {approx} 2.6 days) resulted in a significant decrease in regrowth time in two identical experiments. With results pooled for analysis, the regrowth times for the short and long treatments were 62 and 32 days, respectively (combined p < 0.001). The shorter regrowth times suggest that there was less overall tumor damage with the longer fractionated radiotherapy course. No significant difference in regrowth time was observed in the more slowly proliferating, E{sub 2}-deprived tumors (T{sub pot} {approx} 5.3 days) treated with either the short or long regimen. Median regrowth times were 48 and 54.5 days for the short and long treatments, respectively (combined p = 0.14). Similar changes were observed in regrowth delay. Conclusions: Reduction in the rate of cell proliferation, induced by E{sub 2} deprivation in MCF-7 human breast xenografts during fractionated radiotherapy, resulted in a significantly decreased dependence on overall treatment time in comparison to the more rapidly proliferating E{sub 2}-stimulated tumors. This model suggests that pharmacologically induced reduction in the rate of tumor cell proliferation during a course of fractionated radiotherapy may be a viable alternative to accelerated fractionation for the treatment of rapidly proliferating tumors.}
doi = {10.1016/0360-3016(94)00540-0}
journal = {International Journal of Radiation Oncology, Biology and Physics}
issue = {4}
volume = {31}
journal type = {AC}
place = {United States}
year = {1995}
month = {Feb}
}