Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: The significance of hypoxia on tumor control modelling

被引:37
作者
Buffa, FM
West, C
Byrne, K
Moore, JV
Nahum, AE
机构
[1] Inst Canc Res, Dept Phys, London SW3 6JJ, England
[2] Royal Marsden NHS Trust, London SW3 6JJ, England
[3] Christie Hosp NHS Trust, Paterson Inst, CRC, Expt Radiat Oncol Grp, Manchester M20 4BX, Lancs, England
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2001年 / 49卷 / 04期
关键词
WiDr spheroids; hypoxia; clonogenic cells; tumor control; cell survival assays;
D O I
10.1016/S0360-3016(00)01533-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To evaluate the adequacy of a Poisson tumor control probability (tcp) model and the impact of hypoxia on tumor cure. Methods and Materials: A human colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids df different diameters, Measurements were made of cell survival and spheroid cure following 300-kV X-ray external beam irradiation in air and nitrogen. Cell survival data were fitted using a two-compartment and an oxygen diffusion model. Spheroid cure data were fitted using the icp model. Results: Hypoxia was seen only for spheroids greater than 500 mum in diameter. For small spheroids rep estimates of radiosensitivity and clonogenic number showed excellent agreement with experimentally derived values. For large spheroids, although tcp estimates of radiosensitivity were comparable with measurements, estimates of the clonogenic number were considerably lower than the experimental count. Reoxygenation of large spheroids before irradiation resulted in the icp estimates of the number of clonogenic cells agreeing with measured values. Conclusions: When hypoxia was absent, the tcp model accurately predicted cure from measured radiosensitivity and clonogen number. When hypoxia was present, the number of cells capable of regrowth in situ was considerably lower than the number of clonogenic cells that initially survived irradiation. As this counteracted the decreased radiosensitivity, hypoxia was less important for cure than predicted from cell survival assays. This finding suggests that chronic hypoxia may not Limit directly the success of radiation therapy. (C) 2001 Elsevier Science Inc.
引用
收藏
页码:1109 / 1118
页数:10
相关论文
共 26 条
[1]  
ACKER H, 1987, CANCER RES, V47, P3504
[2]   ROLE OF OXYGEN IN MODIFYING THE RADIOSENSITIVITY OF E-COLI-B [J].
ALPER, T ;
HOWARDFLANDERS, P .
NATURE, 1956, 178 (4540) :978-979
[3]  
BRADLY GW, 1997, RADIAT RES, V147, P541
[4]   A CONVENIENT EXTENSION OF THE LINEAR-QUADRATIC MODEL TO INCLUDE REDISTRIBUTION AND REOXYGENATION [J].
BRENNER, DJ ;
HLATKY, LR ;
HAHNFELDT, PJ ;
HALL, EJ ;
SACHS, RK .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1995, 32 (02) :379-390
[5]   DOSE, VOLUME, AND TUMOR-CONTROL PREDICTIONS IN RADIOTHERAPY [J].
BRENNER, DJ .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1993, 26 (01) :171-179
[6]  
BUFFA FM, 2000, IN PRESS MED PHYS
[7]   Changes in oxygenation during radiotherapy in carcinoma of the cervix [J].
Cooper, RA ;
West, CML ;
Logue, JP ;
Davidson, SE ;
Miller, A ;
Roberts, S ;
Statford, IJ ;
Honess, DJ ;
Hunter, RD .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1999, 45 (01) :119-126
[8]   Vasculature and microenvironmental gradients: The missing links in novel approaches to cancer therapy? [J].
Denekamp, J ;
Dasu, A ;
Waites, A .
ADVANCES IN ENZYME REGULATION, VOL 38, 1998, 38 :281-299
[9]  
Dudewicz E., 1988, MODERN MATH STAT
[10]   Predicting the radiation control probability of heterogeneous tumour ensembles: data analysis and parameter estimation using a closed-form expression [J].
Fenwick, JD .
PHYSICS IN MEDICINE AND BIOLOGY, 1998, 43 (08) :2159-2178