Further analysis of radiobiological parameters from the First and Second British Institute of Radiology randomized studies of larynx/pharynx radiotherapy.

Abstract

This retrospective analysis of 1345 patients treated for cancer of the larynx or pharynx by randomization into two groups in each center in two separate trials of fractionated radiotherapy was carried out in an attempt to extract the radiobiological parameters alpha (dose), beta (fraction size), and gamma (overall time) from the data. Details of the trials have been published previously. In the first, 734 patients were randomized to either five or three fractions per week, in centers each using their own overall time, which varied from 3 to 7 weeks in different centers. In the second trial, 611 patients were randomized to "short" (< or = 4 weeks) or "long" (4-7 weeks) overall time. We combine the data from both studies and use the linear-quadratic formula with logistic regression and maximum-likelihood methods to obtain the radiobiological factors, taking into account other variables such as stage or age, when significant. The parameters calculated for local tumor control showed significant estimates of alpha, very small estimates of beta, and significant values of gamma. The derived estimates of alpha/beta were large, but very variable. The time-dose tradeoff--gamma/alpha was 0.76 Gy/day for larynx and 0.3 Gy/day for pharynx tumors (not significantly different from each other). Late complications gave indeterminate alpha/beta ratios and a time-dose factor not significantly different from zero. Acute normal-tissue effects gave alpha/beta estimates of 8-9 Gy and time factors of 0.8-0.9 Gy/day. The results are consistent with other published values with the exception that significant time factors for late complications could not be excluded.