Author: Shahabeddin mostafanazhad Aslmarand, Lili Chen, Dusica Cvetkovic, Troy A. Dos Santos, Chang Ming Charlie Ma, Dae-Myoung Yang 👨🔬
Affiliation: Fox Chase Cancer Center 🌍
Purpose:
Pulsed low-dose-rate radiotherapy (PLDR) has been proposed to reduce normal tissue toxicity while maintaining tumor control comparable to conventional radiotherapy (CRT). This study assesses PLDR's effectiveness in minimizing normal tissue toxicity in vivo.
Methods:
This study was conducted in three phases. In the first phase, mice underwent single-fraction, total-body irradiation for histological analysis, with data collected 3-and 5-days post-treatment. They were divided into control, PLDR, and CRT groups, receiving doses ranging from 4 to 12Gy. The second phase focused on Whole Abdominal Irradiation (WAI). The lethal dose for WAI was determined under CRT technique and then applied in PLDR settings to compare survival rates and body weight changes. Study was repeated and histological samples were collected at 1,3-,5-,7-, and 9-days post-treatment to assess and compare tissue toxicity. In the third phase, the lethal WAI dose under PLDR conditions was determined.
Results:
Abdominal region was the primary site of distinction between PLDR and CRT. Histological results showed both methods induced a dose-dependent increase in atrophy and hyperplasia; however, CRT resulted in significantly greater tissue toxicity compared to PLDR. In the survival study, the lethal dose of WAI treatment for CRT was 18 Gy. Mice in the CRT group experienced substantial weight loss and succumbed within 9–12 days post-treatment. In contrast, mice in the PLDR group, although initially experiencing weight loss, recovered and survived. Histological findings further confirmed reduced tissue toxicity in the PLDR group. Notably, the lethal dose of WAI for PLDR was 29 Gy—more than 60% higher than that for CRT. This significant difference underscores PLDR's improved tolerance and its potential to provide a greater safety margin in treatment.
Conclusion:
PLDR exhibited lower normal tissue toxicity compared to CRT, offering an advantage in retreatment scenarios where CRT-induced toxicity hampers optimal tumor control.