Repair Kinetics in Mouse Lung after Multiple X-ray Fractions Per Day

Abstract

The potential advantage for sparing normal tissue damage by hyperfractionation of low-LET radiation may be limited by the repair kinetics of tissues in the irradiated field. Tissues with slow repair kinetics will limit the number of fractions that may be given on the same day. Results are presented for mouse lung treated with a range of doses per fraction using either two or three fractions per day in multiple X-ray fractionation schedules. The results are analysed to determine whether the repair kinetics follow a single exponential function of time. The calculated repair rate (T1/2) was about 1.2 h for two fractions per day of 2 Gy (10F/5d) but slightly less (T1/2 = 0.8 h) for two fractions of 9 Gy (2F/1d). For smaller doses per fraction of 1.1 Gy, given three times per day (39F/13d), the T1/2 was not significantly less (T1/2 = 0.3-0.7 h). For three fractions per day of 1.1 Gy per fraction an unsatisfactory fit is achieved using a single exponential function of time, and a better fit is obtained using two components of repair. The repair kinetics are slow for lung, in comparison to acute reacting tissues (except skin), and may require that 6-8 h (i.e. four or five half-times) should be allowed between fractions on the same day so that more than 95 per cent of the repairable dose is repaired. At present the variation in repair kinetics with doses per fraction between 1.1 and 9 Gy are not significantly different, so no reduction of interfraction interval should be proposed.

ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs — Threshold Doses for Tissue Reactions in a Radiation Protection Context

“…In studies where both acute pneumonitis and late fibrosis endpoints were studied, the a=b ratios tended to be slightly lower for fibrosis. Estimates of repair half-time in lung, based on incidence of pneumonitis, are generally in the range of 0.7-1.2 h (Travis et al, 1987;Parkins et al, 1988;Vegesna et al, 1989;Van Rongen et al, 1990a,b). …”

“…In studies where both acute pneumonitis and late fibrosis endpoints were studied, the a=b ratios tended to be slightly lower for fibrosis. Estimates of repair half-time in lung, based on incidence of pneumonitis, are generally in the range of 0.7-1.2 h Parkins et al, 1988;Vegesna et al, 1989;Van Rongen et al, 1990a,b). Some studies have identified two components of repair: a fast component with a half-life of 0.4 h (dominating the effect), and a slow component with a half-life of 4 h (Van Rongen et al, 1993).…”

Potential increase in biological effectiveness from field timing optimization for stereotactic body radiation therapy

“…Though there have been several experiments providing repair rates for normal lung tissue, many of which indicate the presence of both a short and long component of repair, similar analyses for lung tumors do not exist. [16][17][18][19][20][21] One study of normal lung tissue in mice showed that the slower component of repair may approach T 1=2 ¼ 4.0 h. 22 As previously stated, although no evidence indicating similar results in lung tumors exists, if T 1=2 does approach 4.0 h for lung tumors, the effectiveness of this present study would greatly diminish. Nevertheless, Fowler and Chappell did indicate a rapid repopulation of NSCLC during radiation therapy which may imply a fast component of sublethal damage repair.…”

“…As previously stated, studies have indicated that the use of multiple repair half-times are more accurate when studying repair kinetics. [16][17][18][19][20][21] Fowler et al suggested survival fraction calculations using a weighted average of the G-factor. The value of G(t) is calculated for each value of T 1=2 , properly weighted and then added together to get the effective G(t).…”

One- or two-day intervals in conditioning regimens for allo-HCT affect chronic graft-versus-host disease, but not other clinical outcomes

“…However, it is noted that the capacity for toxicity recovery is likely to be decreased more in tumor cells than in normal cells and is expected to be heterogeneous in each type of cancer cell [17][18][19][20]. Moreover, it is not known if the repair capacity of tumor cells recovers in a short period of a few days [21][22][23][24]. Thus, it is challenging to determine whether the interrupted conditioning decreases anti-tumor effects.…”