Superfractionation as a potential hypoxic cell radiosensitizer: Prediction of an optimum dose per fraction

被引:21
作者
Dasu, A [1 ]
Denekamp, J [1 ]
机构
[1] Umea Univ, Dept Oncol, Translat Res Grp, S-90185 Umea, Sweden
来源
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 1999年 / 43卷 / 05期
关键词
hyperfractionation; linear quadratic model; inducible repair; oxygen enhancement ratio; tumor resistance; radiosensitization; computer modeling;
D O I
10.1016/S0360-3016(98)00471-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: A dose "window of opportunity" has been identified in an earlier modeling study (1) if the inducible repair variant of the LQ model is adopted instead of the pure LQ model, and if all survival curve parameters are equally modified by the presence or absence of oxygen. In this paper we have extended the calculations to consider survival curve parameters from 15 sets of data obtained for cells tested at low doses using clonogenic assays. Methods and Materials: A simple computer model has been used to simulate the response of each cell line to various doses per fraction in multifraction schedules, with oxic and hypoxic cells receiving the same fractional dose. We have then used pairs of simulated survival curves to estimate the effective hypoxic protection (OER') as a function of the dose per fraction. Results: The resistance of hypoxic cells is reduced by using smaller doses per fraction than 2 Gy in all these fractionated clinical simulations, whether using a simple LQ model, or the more complex LQ/IR model. If there is no inducible repair, the optimum dose is infinitely low. If there is inducible repair, there is an optimum dose per fraction at which hypoxic protection is minimized. This is usually around 0.5 Gy, It depends on the dose needed to induce repair being higher in hypoxia than in oxygen. The OER' may even go below unity, i.e. hypoxic cells may be more sensitive than oxic cells. Conclusions: If oxic and hypoxic cells are repeatedly exposed to doses of the same magnitude, as occurs in clinical radiotherapy, the observed hypoxic protection varies with the fractional dose. The OER' Is predicted to diminish at lower doses in all cell lines. The loss of hypoxic resistance with superfractionation is predicted to be proportional to the capacity of the cells to induce repair, i.e. their intrinsic radioresistance at a dose of 2 Gy, (C) 1999 Elsevier Science Inc.
引用
收藏
页码:1083 / 1094
页数:12
相关论文
共 58 条
[1]  
ALSBEIH G, RAD RES SOC M 1997
[2]   DOSE FRACTIONATION, DOSE-RATE AND ISO-EFFECT RELATIONSHIPS FOR NORMAL TISSUE RESPONSES [J].
BARENDSEN, GW .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1982, 8 (11) :1981-1997
[3]   RADIOTHERAPY OF THE RHABDOMYOSARCOMA R1H OF THE RAT - HYPERFRACTIONATION - 126 FRACTIONS APPLIED WITHIN 6 WEEKS [J].
BECKBORNHOLDT, HP ;
MAURER, T ;
BECKER, S ;
OMNICZYNSKI, M ;
VOGLER, H ;
WURSCHMIDT, F .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1989, 16 (03) :701-705
[4]   DOSIMETRIC PRECISION REQUIREMENTS IN RADIATION-THERAPY [J].
BRAHME, A .
ACTA RADIOLOGICA ONCOLOGY, 1984, 23 (05) :379-391
[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]   AN UNUSUAL FORM OF RESPONSE IN X-IRRADIATED PROTOZOA AND A HYPOTHESIS AS TO ITS ORIGIN [J].
CALKINS, J .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY AND RELATED STUDIES IN PHYSICS CHEMISTRY AND MEDICINE, 1967, 12 (03) :297-&
[7]   RESPONSES OF 2 MAMMALIAN-CELL LINES TO LOW GAMMA-RAY DOSES [J].
CALKINS, J ;
EINSPENNER, M ;
BLOCHER, D ;
GREER, W .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1989, 56 (06) :869-875
[8]   MOLECULAR THEORY OF CELL SURVIVAL [J].
CHADWICK, KH ;
LEENHOUTS, HP .
PHYSICS IN MEDICINE AND BIOLOGY, 1973, 18 (01) :78-87
[9]   INACTIVATION OF CHINESE-HAMSTER CELLS BY X-RAYS - EFFECTS OF CHEMICAL MODIFIERS ON SINGLE-EVENTS AND DOUBLE-EVENTS [J].
CHAPMAN, JD ;
GILLESPIE, CJ ;
REUVERS, AP ;
DUGLE, DL .
RADIATION RESEARCH, 1975, 64 (02) :365-375