Skip to main content
Log in

Reoxygenation and Split-Dose Response to Radiation in a Tumour Model with Krogh-Type Vascular Geometry

  • Original Article
  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

After a single dose of radiation, transient changes caused by cell death are likely to occur in the oxygenation of surviving cells. Since cell radiosensitivity increases with oxygen concentration, reoxygenation is expected to increase the sensitivity of the cell population to a successive irradiation. In previous papers we proposed a model of the response to treatment of tumour cords (cylindrical arrangements of tumour cells growing around a blood vessel of the tumour). The model included the motion of cells and oxygen diffusion and consumption. By assuming parallel and regularly spaced tumour vessels, as in the Krogh model of microcirculation, we extend our previous model to account for the action of irradiation and the damage repair process, and we study the time course of the oxygenation and the cellular response. By means of simulations of the response to a dose split in two equal fractions, we investigate the dependence of tumour response on the time interval between the fractions and on the main parameters of the system. The influence of reoxygenation on a therapeutic index that compares the effect of a split dose on the tumour and on the normal tissue is also investigated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alarcón, T., Byrne, H.M., Maini, P.K., 2003. A cellular automaton model for tumour growth in inhomogeneous environment. J. Theor. Biol. 225, 257–274.

    Article  Google Scholar 

  • Belli, J.A., Dicus, G.J., Bonte, F.J., 1967. Radiation response of mammalian tumor cells. I. Repair of sublethal damage in vivo. J. Natl. Cancer Inst. 38, 673–682.

    Google Scholar 

  • Bertuzzi, A., d’Onofrio, A., Fasano, A., Gandolfi, A., 2003. Regression and regrowth of tumour cords following single-dose anticancer treatment. Bull. Math. Biol. 65, 903–931.

    Article  Google Scholar 

  • Bertuzzi, A., Fasano, A., Gandolfi, A., 2004. A free boundary problem with unilateral constraints describing the evolution of a tumour cord under the influence of cell killing agents. SIAM J. Math. Anal. 36, 882–915.

    Article  MathSciNet  MATH  Google Scholar 

  • Bertuzzi, A., Fasano, A., Gandolfi, A., Sinisgalli, C., 2007. Cell resensitization after delivery of a cycle-specific anticancer drug and effect of dose splitting: learning from tumour cords. J. Theor. Biol. 244, 388–399.

    Article  MathSciNet  Google Scholar 

  • Brenner, D.J., Hlatky, L.R., Hahnfeldt, P.J., Hall, E.J., Sachs, R.K., 1995. A convenient extension of the linear-quadratic model to include redistribution and reoxygenation. Int. J. Radiat. Oncol. Biol. Phys. 32, 379–390.

    Article  Google Scholar 

  • Bristow, R.G., Hill, R.P., 1998. Molecular and cellular basis of radiotherapy. In: I.F. Tannock, R.P. Hill (Eds.), The Basic Science of Oncology, pp. 295–321. McGraw–Hill, New York.

    Google Scholar 

  • Byrne, H.M., Preziosi, L., 2003. Modelling solid tumour growth using the theory of mixtures. Math. Med. Biol. 20, 341–366.

    Article  MATH  Google Scholar 

  • Casciari, J.J., Sotirchos, S.V., Sutherland, R.M., 1992. Variations in tumor cell growth rates and metabolism with oxygen concentration, glucose concentration, and extracellular pH. J. Cell. Physiol. 151, 386–394.

    Article  Google Scholar 

  • Chapman, J.D., Dougle, D.L., Reuvers, A.P., Meeker, B.E., Borsa, J., 1974. Studies on the radiosensitizing effects of oxygen in Chinese hamster cells. Int. J. Radiat. Biol. 26, 383–389.

    Article  Google Scholar 

  • Crokart, N., Jordan, B.F., Baudelet, C., Ansiaux, R., Sonveaux, P., Grégoire, V., Beghein, N., DeWever, J., Bouzin, C., Feron, O., Gallez, B., 2005. Early reoxygenation in tumors after irradiation: determining factors and consequences for radiotherapy regimens using daily multiple fractions. Int. J. Radiat. Oncol. Biol. Phys. 63, 901–910.

    Google Scholar 

  • Curtis, S.B., 1986. Lethal and potentially lethal lesions induced by radiations—a unified repair model. Radiat. Res. 106, 252–270.

    Article  Google Scholar 

  • Dionysiou, D.D., Stamatakos, G.S., Uzunoglu, N.K., Nikita, K.S., Marioli, A., 2004. A four-dimensional simulation model of tumour response to radiotherapy in vivo: parametric validation considering radiosensitivity, genetic profile and fractionation. J. Theor. Biol. 230, 1–20.

    Article  Google Scholar 

  • Goda, F., O’Hara, J.A., Rhodes, E.S., Liu, K.J., Dunn, J.F., Bacic, G., Swartz, H.M., 1995. Changes of oxygen tension in experimental tumors after a single dose of X-ray irradiation. Cancer Res. 55, 2249–2252.

    Google Scholar 

  • Hirst, D.G., Denekamp, J., 1979. Tumour cell proliferation in relation to the vasculature. Cell Tissue Kinet. 12, 31–42.

    Google Scholar 

  • Hlatky, L.R., Hahnfeldt, P., Sachs, R.K., 1994. Influence of time-dependent stochastic heterogeneity on the radiation response of a cell population. Math. Biosci. 122, 201–220.

    Article  MATH  Google Scholar 

  • Jostes, R.F., Williams, M.E., Barcellos-Hoff, M.H., Hoshino, T., Deen, D.F., 1985. Growth delay in 9L rat brain tumor spheroids after irradiation with single and split doses of X rays. Radiat. Res. 102, 182–189.

    Article  Google Scholar 

  • Kocher, M., Treuer, H., 1995. Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation. Strahlenter. Onkol. 171, 219–230.

    Google Scholar 

  • Kocher, M., Treuer, H., Voges, J., Hoevels, M., Sturm, V., Müller, R.-P., 2000. Computer simulation of cytotoxic and vascular effects of radiosurgery in solid and necrotic brain metastases. Radiother. Oncol. 54, 149–156.

    Article  Google Scholar 

  • Krogh, A., 1919. The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary to supply the tissue. J. Physiol. 52, 409–415.

    Google Scholar 

  • Ljungkvist, A.S.E., Bussink, J., Kaanders, J.H.A.M., Wiedenmann, N.E., Vlasman, R., van der Kogel, A.J., 2006. Dynamics of hypoxia, proliferation and apoptosis after irradiation in a murine tumor model. Radiat. Res. 165, 326–336.

    Article  Google Scholar 

  • Moore, J.V., Hopkins, H.A., Looney, W.B., 1984. Tumour-cord parameters in two rat hepatomas that differ in their radiobiological oxygenation status. Radiat. Environ. Biophys. 23, 213–222.

    Article  Google Scholar 

  • Moore, J.V., Hasleton, P.S., Buckley, C.H., 1985. Tumour cords in 52 human bronchial and cervical squamous cell carcinomas: inferences for their cellular kinetics and radiobiology. Br. J. Cancer 51, 407–413.

    Google Scholar 

  • Obaturov, G.M., Moiseenko, V.V., Filimonov, A.S., 1993. Model of mammalian cell reproductive death. I. Basic assumptions and general equations. Radiat. Environ. Biophys. 32, 285–294.

    Article  Google Scholar 

  • O’Hara, J.A., Goda, F., Demidenko, E., Swartz, H.M., 1998. Effect on regrowth delay in a murine tumor of scheduling split-dose irradiation based on direct pO2 measurements by electron paramagnetic resonance oximetry. Radiat. Res. 150, 549–556.

    Article  Google Scholar 

  • Popel, A.S., 1989. Theory of oxygen transport to tissue. Crit. Rev. Biomed. Eng. 17, 257–321.

    Google Scholar 

  • Ribba, B., Colin, T., Schnell, S., 2006. A multiscale mathematical model of cancer, and its use in analyzing irradiation therapies. Theor. Biol. Med. Model. 3, 7, doi: 10.1186/1742-4682-3-7.

    Article  Google Scholar 

  • Sachs, R.K., Hahnfeld, P., Brenner, D.J., 1997. The link between low-LET dose-response relations and the underlying kinetics of damage production/repair/misrepair. Int. J. Radiat. Biol. 72, 351–374.

    Article  Google Scholar 

  • Secomb, T.W., Hsu, R., Dewhirst, M.W., Klitzman, B., Gross, J.F., 1993. Analysis of oxygen transport to tumor tissue by microvascular networks. Int. J. Radiat. Oncol. Biol. Phys. 25, 481–489.

    Google Scholar 

  • Sonveaux, P., Dessy, C., Brouet, A., Jordan, B.F., Grégoire, V., Gallez, B., Balligard, J.L., Feron, O., 2002. Modulation of the tumor vasculature functionality by ionizing radiation accounts for tumor radiosensitization and promotes gene delivery. FASEB J. 16, 1979–1981.

    Google Scholar 

  • Tannock, I.F., 1968. The relation between cell proliferation and the vascular system in a transplanted mouse mammary tumour. Br. J. Cancer 22, 258–273.

    Google Scholar 

  • Thames, H.D., 1985. An ‘incomplete-repair’ model for survival after fractionated and continuous irradiations. Int. J. Radiat. Biol. 47, 319–339.

    Article  Google Scholar 

  • Vaupel, P., Frinak, S., O’Hara, M., 1984. Direct measurement of reoxygenation in malignant mammary tumors after a single large dose of irradiation. Adv. Exp. Med. Biol. 180, 773–782.

    Google Scholar 

  • Wong, C.S., Hill, R.P., 1998. Experimental radiotherapy. In: I.F. Tannock, R.P. Hill (Eds.), The Basic Science of Oncology, pp. 322–349. McGraw–Hill, New York.

    Google Scholar 

  • Wouters, B.G., Brown, J.M., 1997. Cells at intermediate oxygen levels can be more important than the “hypoxic fraction” in determining tumor response to fractionated radiotherapy. Radiat. Res. 147, 541–550.

    Article  Google Scholar 

  • Zhao, M., Pipe, J.G., Bonnett, J., Evelhoch, J.L., 1996. Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy in a murine tumour in vivo. Br. J. Cancer 73, 61–64.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Bertuzzi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bertuzzi, A., Fasano, A., Gandolfi, A. et al. Reoxygenation and Split-Dose Response to Radiation in a Tumour Model with Krogh-Type Vascular Geometry. Bull. Math. Biol. 70, 992–1012 (2008). https://doi.org/10.1007/s11538-007-9287-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11538-007-9287-9

Keywords

Navigation