Manchester Cancer Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, UK; University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, UK.
University of Manchester, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, UK.
Radiother Oncol. 2020 Nov;152:177-182. doi: 10.1016/j.radonc.2020.04.008. Epub 2020 Apr 14.
A recent study of NSCLC patients showed small residual setup errors (shifts) in the direction of the heart following image-guidance were significantly related to overall survival. This study of the dosimetric effects of these residual shifts investigates the hypothesis that observed survival differences were related to a change in heart dose.
Accumulated doses including shifts for each fraction were determined for 475 NSCLC patients. Planning CTs and corresponding dose distributions were deformed to a reference. Image-based data-mining techniques were then applied to the difference between the planned and accumulated dose (Δdose) to determine where Δdose relates to 1-year survival. The significance of Δdose in the identified region was assessed using multivariable Cox analysis. The cohort was then split into octiles, based upon planned dose to the region, and multivariable Cox analysis performed for each sub-cohort to explore the dose response relationship. The identified dose threshold for damage was then tested in an independent validation cohort of 1482 NSCLC patients from the same institution.
Permutation testing identified a small region in the heart base where Δdose significantly correlated with 1-year survival. Δdose in this region showed no correlation with common clinical variables, and was significant in multivariable Cox regression (p < 0.001, hazard ratio 1.221/Gy), with increasing change in dose from plan resulting in greater risk of death. Octile analysis revealed Δdose to be significant only in the 7th octile, planning dose 16.2-23.4 Gy, suggesting a steep dose-effect relation for heart damage in this range. Taking 16.2 Gy as a conservative threshold dose, this result was successfully validated, with a significant difference being seen between patients with a region dose above or below 16.2 Gy.
This study suggests the relation between residual set-up errors and survival is explained by changes in cardiac dose, and identifies an area at the heart base where dose is correlated with survival. Our results suggest the dose threshold for cardiac damage is between 16.2 and 23.4 Gy in the base of the heart, which was validated in an independent cohort. However, the dose effect in other regions of the heart should also be investigated.
最近一项针对非小细胞肺癌（NSCLC）患者的研究表明，在图像引导下，心脏方向的微小残余摆位误差（移位）与总生存显著相关。本研究调查了这些残余移位的剂量学效应，假设观察到的生存差异与心脏剂量的变化有关。
为 475 例 NSCLC 患者确定了每个分次的累积剂量，包括移位。将计划 CT 及其相应的剂量分布变形至参考值。然后，应用基于图像的数据挖掘技术来确定计划剂量与累积剂量（Δ剂量）之间的差异，以确定 Δ剂量与 1 年生存率的关系。采用多变量 Cox 分析评估所确定区域中 Δ剂量的显著性。然后，根据该区域的计划剂量将队列分为 8 个等分位数，并对每个子队列进行多变量 Cox 分析，以探讨剂量反应关系。然后，在来自同一机构的 1482 例 NSCLC 患者的独立验证队列中测试所确定的损伤剂量阈值。
随机检验确定了心脏基底的一个小区域，其中 Δ剂量与 1 年生存率显著相关。该区域的 Δ剂量与常见临床变量无关，在多变量 Cox 回归中具有统计学意义（p<0.001，风险比 1.221/Gy），随着计划剂量的增加，死亡风险增加。八进制分析显示，仅在第 7 个八进制，即计划剂量 16.2-23.4 Gy 时，Δ剂量具有统计学意义，提示在此范围内心脏损伤存在陡峭的剂量效应关系。将 16.2 Gy 作为保守的剂量阈值，该结果得到了成功验证，剂量高于或低于 16.2 Gy 的患者之间存在显著差异。
本研究表明，残余摆位误差与生存之间的关系可通过心脏剂量的变化来解释，并确定了心脏基底与生存相关的剂量区域。我们的结果表明，心脏损伤的剂量阈值在心脏基底的 16.2 至 23.4 Gy 之间，在独立队列中得到了验证。然而，还应研究心脏其他区域的剂量效应。
