大肿瘤大小已经被报道为碳离子放射治疗（CIRT）中预示不良临床结果的预测因素。除了伴随这些肿瘤的临床因素外，较大的肿瘤通常会接收更多的低线性能量转移（LET）贡献，这可能是潜在的物理原因。尽管剂量平均LET常用作一个单参数描述符来量化束质量，但没有证据表明该参数是CIRT中复杂混合辐射场的最佳临床预测因子。本研究的目的是研究一种新的剂量学量，即高LET剂量（D > L thr，基于LET阈值过滤的物理剂量），作为一个单参数估计器来区分小肿瘤和大肿瘤的碳离子治疗计划（cTP）。选择了十个计划目标体积（PTV）大于等于500cm^3（大）的cTP和九个PTV小于500cm^3（小）的cTP用于本研究。为了找到一个合理的LET阈值（L thr），以便在D > L thr分布上产生显著差异，使用标准分布描述符（均值、方差和偏度）研究了临床靶体积（CTV）中基于体素的归一化高LET剂量（ D ̂ > L thr）在一个子集（19个cTP中的12个）上的分布,在固定的L_{thr}上评估了所有19个cTP目标中D > L_{thr}和 D ̂ > L_{thr}的剂量容积直方图参数，采用（双侧）t检验或Mann-Whitney U检验评估两组之间平均D > L_{thr}和D ̂ > L_{thr}的统计学显著性差异。此外，将在上述确定的L thr上的最小目标覆盖进行比较和验证，以验证其在区分小体积和大体积肿瘤中的潜力。发现大约30\ keV /μm的L thr是合理的阈值，可以对两组进行分类。在此阈值下，小CTV中的D > L_{thr}和 D ̂ > L_{thr}（p < 0.05）显著较大。对于小肿瘤组，CTV中的近最小和中位D > L_{thr}（和 D ̂ > L_{thr}）平均分别为9.3 ± 1.5\ Gy（0.31 ± 0.08）和13.6 ± 1.6\ Gy（0.46 ± 0.06）。对于大肿瘤，这些参数分别为6.6 ± 0.2\ Gy（0.20 ± 0.01）和8.6 ± 0.4\ Gy（0.28 ± 0.02）。在平均近最小和中位D > L_{thr}（D ̂ > L_{thr}）方面，两组之间的差异为2.7\ Gy（11%）和5.0\ Gy（18%）。这项研究显示了基于高LET剂量的评估的可行性，其中在肿瘤体积较大的cTP中发现了较低的D > L_{thr}。需要进一步的研究来得出临床结论。本研究中提出的方法可以应用于未来基于高LET剂量的研究。© 2023 The Authors. Medical Physics由Wiley Periodicals LLC代表美国医学物理学家协会出版。

Large tumor size has been reported as a predicting factor for inferior clinical outcome in carbon ion radiotherapy (CIRT). Besides the clinical factors accompanied with such tumors, larger tumors receive typically more low linear energy transfer (LET) contributions than small ones which may be the underlying physical cause. Although dose averaged LET is often used as a single parameter descriptor to quantify the beam quality, there is no evidence that this parameter is the optimal clinical predictor for the complex mixed radiation fields in CIRT.Purpose of this study was to investigate on a novel dosimetric quantity, namely high-LET-dose ( D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ , the physical dose filtered based on an LET threshold) as a single parameter estimator to differentiate between carbon ion treatment plans (cTP) with a small and large tumor volume.Ten cTPs with a planning target volume, PTV ≥ 500 cm 3 $\mathrm{PTV}\ge {500}\,{{\rm cm}^{3}}$ (large) and nine with a PTV < 500 cm 3 $\mathrm{PTV}<{500}\,{{\rm cm}^{3}}$ (small) were selected for this study. To find a reasonable LET threshold ( L thr $\textrm {L}_{\textrm {thr}}$ ) that results in a significant difference in terms of D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ , the voxel based normalized high-LET-dose ( D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ ) distribution in the clinical target volume (CTV) was studied on a subset (12 out of 19 cTPs) for 18 LET thresholds, using standard distribution descriptors (mean, variance and skewness). The classical dose volume histogram concept was used to evaluate the D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ distributions within the target of all 19 cTPs at the before determined L thr $\textrm {L}_{\textrm {thr}}$ . Statistical significance of the difference between the two groups in terms of mean D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ volume histogram parameters was evaluated by means of (two-sided) t-test or Mann-Whitney-U-test. In addition, the minimum target coverage at the above determined L thr $\textrm {L}_{\textrm {thr}}$ was compared and validated against three other thresholds to verify its potential in differentiation between small and large volume tumors.An L thr $\textrm {L}_{\textrm {thr}}$ of approximately 30 keV / μ m ${30}\,{\rm keV/}\umu {\rm m}$ was found to be a reasonable threshold to classify the two groups. At this threshold, the D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ and D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ were significantly larger ( p < 0.05 $p<0.05$ ) in small CTVs. For the small tumor group, the near-minimum and median D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ (and D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ ) in the CTV were in average 9.3 ± 1.5 Gy $9.3\pm {1.5}\,{\rm Gy}$ (0.31 ± 0.08) and 13.6 ± 1.6 Gy $13.6\pm {1.6}\,{\rm Gy}$ (0.46 ± 0.06), respectively. For the large tumors, these parameters were 6.6 ± 0.2 Gy $6.6\pm {0.2}\,{\rm Gy}$ (0.20 ± 0.01) and 8.6 ± 0.4 Gy $8.6\pm {0.4}\,{\rm Gy}$ (0.28 ± 0.02). The difference between the two groups in terms of mean near-minimum and median D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ ( D ̂ > L thr $\hat{\textrm {D}}_{>\textrm {L}_{\textrm {thr}}}$ ) was 2.7 Gy (11%) and 5.0 Gy (18%), respectively.The feasibility of high-LET-dose based evaluation was shown in this study where a lower D > L thr $\textrm {D}_{>\textrm {L}_{\textrm {thr}}}$ was found in cTPs with a large tumor size. Further investigation is needed to draw clinical conclusions. The proposed methodology in this work can be utilized for future high-LET-dose based studies.© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.