Purpose:Pulsed low dose rate radiotherapy (PLDR) is a radiotherapy approach expected to reduce normal tissue toxicity while maintaining equivalent tumor control as conventional radiotherapy (CRT). This preliminary study evaluates the effectiveness of PLDR in reducing normal tissue toxicity in vivo.Materials and Methods:In the initial phase, C57BL/6 mice underwent histological examination following single-fraction, total-body irradiation. Observations were conducted at 3 and 5 days post-treatment. Mice were divided into control, PLDR, and CRT groups, receiving varying doses ranging from 4 to 12 Gy. Building upon the histological findings, the second phase centered on whole-abdominal irradiation (WAI) and determining the lethal dose for WAI using CRT. Subsequently, this dose was applied in PLDR settings to compare survival rates and changes in body weight. The experiment was replicated to collect histology samples at 1-, 3-, 5-, 7-, and 9-day endpoints, enabling the assessment and comparison of tissue toxicity. Finally, exploration into PLDR’s lethal WAI dose was conducted.Results:Histology results showed the abdominal region as the main site of difference between PLDR and CRT, with both methods causing a dose-dependent increase in atrophy and hyperplasia. However, CRT led to higher tissue toxicity compared to PLDR. In the survival study, the fatal dose for WAI treatment was 18 Gy, with mice in the CRT group experiencing substantial weight loss and dying within 9–12 days post-treatment. In contrast, mice in the PLDR group, despite an initial weight loss, recovered their weight and survived. Histology results also showed that the PLDR group had less tissue toxicity. Furthermore, the fatal dose of WAI for PLDR was revealed to be 29 Gy, which is over 60% higher than the dose required for CRT, indicating a substantial difference in tolerance and potential safety margin provided by PLDR treatment.Conclusions:PLDR demonstrated a reduced normal toxicity compared to CRT, potentially beneficial in re-treatment scenarios or for tumors where CRT-induced toxicity limits tumor control, such as in liver cases.
目的：脉冲低剂量率放疗（PLDR）是一种旨在降低正常组织毒性，同时保持与传统放疗（CRT）等效肿瘤控制的放疗方法。本初步研究评估了PLDR在体内降低正常组织毒性的有效性。 材料与方法：在第一阶段，C57BL/6小鼠在接受单次全身照射后进行组织学检查。观察在治疗后第3天和第5天进行。小鼠被分为对照组、PLDR组和CRT组，接受从4 Gy到12 Gy不等的剂量照射。基于组织学发现，第二阶段聚焦于全腹部照射（WAI），并使用CRT确定WAI的致死剂量。随后，将此剂量应用于PLDR设置中，以比较生存率和体重变化。实验进行了重复，并在第1、3、5、7和9天终点收集组织学样本，以便评估和比较组织毒性。最后，对PLDR的WAI致死剂量进行了探索。 结果：组织学结果显示，腹部区域是PLDR与CRT产生差异的主要部位，两种方法均导致萎缩和增生呈剂量依赖性增加。然而，与PLDR相比，CRT导致了更高的组织毒性。在生存研究中，WAI治疗的致死剂量为18 Gy，CRT组小鼠在治疗后9-12天内体重显著下降并死亡。相比之下，PLDR组小鼠尽管初期体重下降，但体重得以恢复并存活。组织学结果也显示PLDR组的组织毒性较低。此外，研究发现PLDR的WAI致死剂量为29 Gy，比CRT所需剂量高出60%以上，这表明PLDR治疗在耐受性和潜在安全边际方面存在显著差异。 结论：与CRT相比，PLDR表现出更低的正常组织毒性，这可能对再治疗场景或因CRT诱导的毒性（例如在肝脏病例中）而限制肿瘤控制的肿瘤有益。
Investigation of Normal Tissue Toxicity in Pulsed Low Dose Rate Radiotherapy
肿瘤(癌症)患者之家