In silico Repopulation Model of Various Tumour Cells during Treatment Breaks in Head and Neck Cancer Radiotherapy

Advanced head and neck cancers are aggressive
tumours, which require aggressive treatment. Treatment efficiency is
often hindered by cancer cell repopulation during radiotherapy,
which is due to various mechanisms triggered by the loss of tumour
cells and involves both stem and differentiated cells. The aim of the
current paper is to present in silico simulations of radiotherapy
schedules on a virtual head and neck tumour grown with biologically
realistic kinetic parameters. Using the linear quadratic formalism of
cell survival after radiotherapy, altered fractionation schedules
employing various treatment breaks for normal tissue recovery are
simulated and repopulation mechanism implemented in order to
evaluate the impact of various cancer cell contribution on tumour
behaviour during irradiation. The model has shown that the timing of
treatment breaks is an important factor influencing tumour control in
rapidly proliferating tissues such as squamous cell carcinomas of the
head and neck. Furthermore, not only stem cells but also
differentiated cells, via the mechanism of abortive division, can
contribute to malignant cell repopulation during treatment.

• Loredana G. Marcu
• David Marcu
• Sanda M. Filip

• Radiation
• tumour repopulation
• squamous cell carcinoma
• stem cell.

[1] H. R. Withers, “Treatment-induced accelerated human tumor growth”, Semin. Radiat. Oncol., vol. 3, no. 2, pp. 135-143, Apr. 1993.
[2] W. Dorr, “Modulation of repopulation processes in oral mucosa: experimental results,” Int. J. Radiat.Biol.,vol 79, no. 7, pp. 531-537, Jul. 2003.
[3] K. Fu, T. Pajak, A. Trotti, C. U. Jones, S. A. Spence, T. Phillips, et al., “A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003,” Int. J. Radiat. Oncol. Biol. Phys., vol. 48, no. 1, pp. 7-16, Aug. 2000.
[4] L. Marcu, T. van Doorn, I. Olver and S. Zavgorodni, “Growth of a virtual tumour using probabilistic methods of cell generation,” Australas. Phys. Eng. Sci. Med., vol. 25, no. 4, pp. 155-161, Dec. 2002. [5] I. Tannock and R. Hill 1998 The basic science of oncology. 3rd ed, New York: McGraw-Hill, 1998, pp. 357-392.
[6] S. M. Bentzen and M. Baumann, “The linear-quadratic model in clinical practice,” inBasic clinical radiobiology,3rd ed., G. G. Steel, Ed. London: Arnold Publisher; 2002. p. 134-146.