The Division of Cancer Science, The University of Manchester, Manchester, United Kingdom; The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
The Division of Cancer Science, The University of Manchester, Manchester, United Kingdom; The Christie National Health Service (NHS) Foundation Trust, Manchester, United Kingdom.
J Thorac Oncol. 2023 May;18(5):599-607. doi: 10.1016/j.jtho.2023.01.085. Epub 2023 Feb 3.
The RTOG 0617 trial presented a worse survival for patients with lung cancer treated in the high-dose (74 Gy) arm. In multivariable models, radiation level and whole-heart volumetric dose parameters were associated with survival. In this work, we consider heart subregions to explain the observed survival difference between radiation levels.
Voxel-based analysis identified anatomical regions where the dose was associated with survival. Bootstrapping clinical and dosimetric variables into an elastic net model selected variables associated with survival. Multivariable Cox regression survival models assessed the significance of dose to the heart subregion, compared with whole heart v5 and v30. Finally, the trial outcome was assessed after propensity score matching of patients on lung dose, heart subregion dose, and tumor volume.
A total of 458 patients were eligible for voxel-based analysis. A region of significance (p < 0.001) was identified in the base of the heart. Bootstrapping selected mean lung dose, radiation level, log tumor volume, and heart region dose. The multivariable Cox model exhibited dose to the heart region (p = 0.02), and tumor volume (p = 0.03) were significantly associated with survival, and radiation level was not significant (p = 0.07). The models exhibited that whole heart v5 and v30 were not associated with survival, with radiation level being significant (p < 0.05). In the matched cohort, no significant survival difference was seen between radiation levels.
Dose to the base of the heart is associated with overall survival, partly removing the radiation level effect, and explaining that worse survival in the high-dose arm is owing, in part, to the heart subregion dose. By defining a heart avoidance region, future dose escalation trials may be feasible.
RTOG 0617 试验表明，接受高剂量（74 Gy）治疗的肺癌患者的生存情况更差。在多变量模型中，放射剂量和整个心脏体积剂量参数与生存相关。在这项工作中，我们考虑心脏亚区来解释观察到的放射剂量水平之间的生存差异。
体素分析确定了与生存相关的剂量的解剖区域。通过将临床和剂量学变量引导到弹性网络模型中，选择与生存相关的变量。多变量 Cox 回归生存模型评估了心脏亚区剂量与整个心脏 v5 和 v30 相比对生存的重要性。最后，通过对肺剂量、心脏亚区剂量和肿瘤体积的倾向评分匹配，评估试验结果。
共有 458 名患者符合体素分析的条件。在心底部发现了一个有意义的区域（p<0.001）。引导选择平均肺剂量、放射水平、对数肿瘤体积和心脏区域剂量。多变量 Cox 模型显示心脏区域剂量（p=0.02）和肿瘤体积（p=0.03）与生存显著相关，而放射水平不显著（p=0.07）。模型显示，整个心脏 v5 和 v30 与生存无关，而放射水平有意义（p<0.05）。在匹配队列中，放射水平之间没有显著的生存差异。
心脏底部的剂量与总生存相关，部分消除了放射水平的影响，并解释了高剂量组生存较差的部分原因是心脏亚区剂量。通过定义心脏回避区域，未来的剂量递增试验可能是可行的。
