Antonovic Laura, Lindblom Emely, Dasu Alexandru, Bassler Niels, Furusawa Yoshiya, Toma-Dasu Iuliana
Department of Physics, Stockholm University, Stockholm, Sweden
Department of Physics, Stockholm University, Stockholm, Sweden.
J Radiat Res. 2014 Sep;55(5):902-11. doi: 10.1093/jrr/rru020. Epub 2014 Apr 11.
The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account, using the repairable-conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high level of tumor control probability is achievable with a large range of fractionation schedules for tumors with hypoxic subvolumes, but both hyperfractionation and hypofractionation should be pursued with caution.
由于扩展布拉格峰（SOBP）中的线性能量传递（LET）值较低，碳离子放射治疗对缺氧肿瘤的效果最近受到质疑。本研究的目的是探讨缺氧和局部氧合变化（LOCs）在分次碳离子放射治疗中的作用。假设分次间存在LOCs，模拟了具有缺氧子体积的三维肿瘤。使用具有已知LET分布的临床相关治疗计划应用不同的分割方式。考虑到氧张力、剂量和LET，使用具有人类唾液腺肿瘤细胞参数的可修复-条件可修复（RCR）损伤模型计算存活分数。临床氧增强比（OER）定义为缺氧和氧合良好的肿瘤达到50%肿瘤控制概率所需剂量的比值。所有分割方式得到的OER均远高于1。对于缺氧肿瘤，如果假设存在LOCs而不是静态氧合，则肿瘤控制概率会显著更高。LOCs的有益效果随着分割次数的增加而增加。然而，对于非常低的分割剂量，与LOCs相关的改善并不能弥补肿瘤控制所需总剂量的增加。总之，我们的结果表明，由于SOBP中低LET下不可忽略的氧效应，缺氧会影响碳离子放射治疗的结果。然而，如果发生LOCs，对于具有缺氧子体积的肿瘤，在大范围的分割方案下可以实现相对较高水平的肿瘤控制概率，但超分割和低分割都应谨慎采用。
