The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters
The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters
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DOI：
10.1002/mp.14381
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发表时间：
2020-08-02
期刊：
影响因子：
3.8
通讯作者：
Umegaki, Kikuo
中科院分区：
文献类型：
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作者：
Kasamatsu, Koki;Matsuura, Taeko;Umegaki, Kikuo
目的采用生物物理模型，以细胞特异性参数（α/β）（x）和T（1/2）（修复半衰期）评价质子长时间照射对亚致死损伤（SLD）的修复作用。目前，大多数基于模型的质子研究都集中在急性辐射上，忽略了在辐射输送过程中由于SLD修复而导致的生物学有效性降低。然而，随着先进的治疗技术（如低分割和呼吸门控）进入临床实践，生物有效性的剂量率依赖性可能变得更加重要，因为这些技术有时需要较长的治疗时间。此外，虽然以前的研究使用生物物理模型揭示了一个大的修复效果与高物理剂量，修复效果对细胞特异性参数的依赖性尚未得到系统的评估。方法采用线性能量传递（LET）依赖的线性二次型（LQ）模型，结合双辐射作用（TQ）理论，计算含修复的生物剂量[相对生物学效应（RBE）×物理剂量]。首先，我们扩展了剂量延长因子在LQ模型中的任意数量的不同的LET质子照射顺序提供任意的时间滞后，参考TQs。使用LQ模型，系统评价了在水模体中进行扩展布拉格峰（SOBP）辐照时，由于SLD修复导致的生物剂量降低，其中（α/β）（x）和修复参数的可能范围（（α/β）（x）= 1-15戈伊，T-1/2 = 0-90 min）。然后，考虑到更现实的辐射条件，前列腺，肝脏和肺肿瘤的临床病例进行了检查，从文献中获得的每个肿瘤的细胞特异性参数。生物学D（99%）和生物剂量均匀性系数（HC）计算的临床靶体积（CTVs），假设总照射时间为0-60 min的剂量率结构。结果细胞特异性参数的差异导致相当大的变化在修复效果。当（α/β）（x）固定为10戈伊时，连续照射30 min，在SOBP中心发现的生物剂量减少在1.13%至14.4%之间变化，aT（1/2）范围为1-90 min。对于T（1/2）= 30 min的固定值，其变化范围为2.3%至6.8%，（α/β）（x）范围为1-15戈伊。对于前列腺、肝脏和肺部肿瘤病例，每10 min生物D（99%）的降低分别为2.6%、1.2%和3.0%。生物学D（99%）降低值既不是（α/β）（x）的顺序，也不是处方剂量的顺序，但两者都有助于修复效果。所有病例的HC变化均在0.5%范围内;因此，剂量分布未失真。结论SLD修复引起的生物剂量降低除物理剂量外，还与细胞特异性参数有关。在评价长时间质子照射的修复效果时，应仔细考虑这些参数。
Purpose The purpose of this study is to evaluate the sublethal damage (SLD) repair effect in prolonged proton irradiation using the biophysical model with various cell-specific parameters of (alpha/beta)(x)andT(1/2)(repair half time). At present, most of the model-based studies on protons have focused on acute radiation, neglecting the reduction in biological effectiveness due to SLD repair during the delivery of radiation. Nevertheless, the dose-rate dependency of biological effectiveness may become more important as advanced treatment techniques, such as hypofractionation and respiratory gating, come into clinical practice, as these techniques sometimes require long treatment times. Also, while previous research using the biophysical model revealed a large repair effect with a high physical dose, the dependence of the repair effect on cell-specific parameters has not been evaluated systematically. Methods Biological dose [relative biological effectiveness (RBE) x physical dose] calculation with repair included was carried out using the linear energy transfer (LET)-dependent linear-quadratic (LQ) model combined with the theory of dual radiation action (TDRA). First, we extended the dose protraction factor in the LQ model for the arbitrary number of different LET proton irradiations delivered sequentially with arbitrary time lags, referring to the TDRA. Using the LQ model, the decrease in biological dose due to SLD repair was systematically evaluated for spread-out Bragg peak (SOBP) irradiation in a water phantom with the possible ranges of both (alpha/beta)(x)and repair parameters ((alpha/beta)(x) = 1-15 Gy,T-1/2 = 0-90 min). Then, to consider more realistic irradiation conditions, clinical cases of prostate, liver, and lung tumors were examined with the cell-specific parameters for each tumor obtained from the literature. BiologicalD(99%)and biological dose homogeneity coefficient (HC) were calculated for the clinical target volumes (CTVs), assuming dose-rate structures with a total irradiation time of 0-60 min. Results The differences in the cell-specific parameters resulted in considerable variation in the repair effect. The biological dose reduction found at the center of the SOBP with 30 min of continuous irradiation varied from 1.13% to 14.4% with aT(1/2)range of 1-90 min when (alpha/beta)(x)is fixed as 10 Gy. It varied from 2.3% to 6.8% with an (alpha/beta)(x)range of 1-15 Gy for a fixed value ofT(1/2) = 30 min. The decrease in biologicalD(99%)per 10 min was 2.6, 1.2, and 3.0% for the prostate, liver, and lung tumor cases, respectively. The value of the biologicalD(99%)reduction was neither in the order of (alpha/beta)(x)nor prescribed dose, but both comparably contributed to the repair effect. The variation of HC was within the range of 0.5% for all cases; therefore, the dose distribution was not distorted. Conclusion The reduction in biological dose caused by the SLD repair largely depends on the cell-specific parameters in addition to the physical dose. The parameters should be considered carefully in the evaluation of the repair effect in prolonged proton irradiation.