Late radiation response of the canine trachea with change in dose per fraction.

Seventy-two dogs were given 36 to 74 Gy to the trachea in either 2, 3, or 4 Gy per fraction. Tracheal sections were histologically and morphometrically evaluated 6 months after irradiation to determine the relative percentage of goblet cells, submucosal glands, connective tissue and blood vessels. The percent of each tissue component was plotted against total dose, regression lines calculated and isoeffective doses obtained for construction of isoeffect curves. Probit analysis for probability of surface ulceration also was done. Another group of 32 dogs received either 36, 44, or 52 Gy in 4 Gy fractions and tracheas were similarly analyzed at 1, 3, and 12 months after irradiation. Goblet cells and submucosal glands decreased with increasing total dose in each of the dose per fraction groups while connective tissue increased. Lower doses per fraction had more shallow dose response curves and higher total doses were required to produce an isoeffect. The alpha/beta ratios for tissues at 6 months after irradiation were 3.5 Gy for decrease in goblet cells, 4.7 Gy for probability for surface ulceration, 4.5 Gy for decrease in submucosal glands and 1.8 Gy for increase in connective tissue. Goblet cells and submucosal gland numbers decreased within 1 month and remained significantly decreased at higher doses at 12 months. Although there was no dose response for vasculature volume at 6 months, significant perivascular and intimal fibrosis was observed. This study revealed significant damage to the trachea at high total doses and large doses per fraction. The relatively low alpha/beta ratios obtained indicates that these adverse effects are late effects. Significant sparing of the adverse late effects was present at lower doses per fraction. These results indicate that coarser fractionation schemes that include the trachea in the treatment volume could be potentially dangerous.