Influence of radiotherapy treatment time on control of laryngeal cancer: Comparisons between centres in Manchester, UK and Toronto, Canada

A comparison has been made of the influence of treatment time on tumour control rates for 496 (T2 and T3) larynx cancer cases in Manchester, UK and 1001 (T1-T4) cases in Toronto, Canada. Both series of patients were treated in fairly short overall times, commonly 3 weeks in Manchester and 4-5 weeks in Toronto. All the tumour control data were analysed using the same method to obtain values of fitted dose, fractionation and time parameters. The analysis showed the following. (a) Differences between the total combined (T2 + T3) data sets from the two centres, fitted using direct analysis and the LQ model incorporating a parameter for overall treatment time, were not significant (p = 0.17) and close similarity in control rates was observed using treatment regimens common to both series. (b) The Manchester series over 9-41 days and the Toronto series over 14-84 days are both consistent in showing for (T2 + T3) tumours the presence of a mean time factor of 0.6- 0.8 Gy/day required to abrogate the decrease in tumour control concomitant with an increase in overall treatment time from the minimum to the maximum employed in each series. (c) When a parameter was included in the model to test for the possible presence of a lag period before the time factor became operative, the lag was not significant for the Toronto data, in contrast to a significant lag for the Manchester data alone (T2 + T3 data). Hence, even with the large combined number of 1073 (T2 + T3) patients from the two centres it was not possible to resolve separate time factors for different periods of the overall treatment times. Also, there was no significant difference overall between the responses of glottic versus supraglottic tumours. (d) The data for all stages (T1-T4) in Toronto and T3 (but not T2) in Manchester are compatible with considerable heterogeneity among the population of tumours which results in a fairly flat dose-response curve (mean D(a) about 30 Gy, albeit with very wide confidence intervals). Hence the time factor could be interpreted as a reflection of a low 'effective' rate of increase in tumour clonogen number during treatment for the population of patients as a whole, with a higher and unknown rate for individual patients.