探究接受光子和质子治疗的局部晚期非小细胞肺癌患者的心包积液和死亡率与胸腔剂量模式的关系。
Probing thoracic dose patterns associated to pericardial effusion and mortality in patients treated with photons and protons for locally advanced non-small-cell lung cancer.
机构信息
National Research Council, Institute of Biostructures and Bioimaging, Napoli, Italy.
National Research Council, Institute of Biostructures and Bioimaging, Napoli, Italy.
出版信息
Radiother Oncol. 2021 Jul;160:148-158. doi: 10.1016/j.radonc.2021.04.025. Epub 2021 May 9.
PURPOSE
To investigate thoracic dose-response patterns for pericardial effusion (PCE) and mortality in patients treated for locally advanced Non-Small-Cell Lung Cancer (NSCLC) by Intensity Modulated RT (IMRT) or Passive-Scattering Proton Therapy (PSPT).
METHODS
Among 178 patients, 43.5% developed grade ≥ 2 PCE. Clinical and dosimetric factors associated with PCE or overall survival (OS) were identified via multi-variable Cox proportional hazards modeling. The Voxel-Based Analyses (VBAs) of local dose differences between patients with and without PCE and mortality was performed. The robustness of VBA results was assessed by a novel characterization of spatial properties of dose distributions based on probabilistic independent component analysis (PICA) and connectograms.
RESULTS
Several non-dosimetric variables were selected by the multivariable analysis for the considered outcomes, while the time-dependent PCE onset was uncorrelated with the OS (p = 0.34) at a multi-variable Cox analysis. Despite the significant PSPT dosimetric advantage, the RT technique did not affect the occurrence of PCE or OS. VBAs highlighted largely overlapping clusters significantly associated with PCE endpoints in heart and lungs. No significant dosimetric patterns related to mortality endpoints were found. PICA identified 43 components homogeneously scattered within thorax, while connectograms showed modest correlations between doses in main cardio-pulmonary substructures.
CONCLUSIONS
Spatially resolved analysis highlighted dose patterns related to radiation-induced cardiac toxiciy and the observed organ-based dose-response mismatch in PSPT and IMRT. Indeed, the thoracic regions spared by PSPT poorly overlapped with the areas involved in PCE development, as highlited by VBA. PICA and connectograms proved valuable tools for assessing the robusteness of obtained VBA inferences.
目的
通过调强放射治疗（IMRT）或被动散射质子治疗（PSPT）治疗局部晚期非小细胞肺癌（NSCLC）的患者，研究心包积液（PCE）和死亡率的胸部剂量反应模式。
方法
在 178 名患者中，有 43.5%的患者出现了≥2 级 PCE。通过多变量 Cox 比例风险模型确定与 PCE 或总生存（OS）相关的临床和剂量学因素。对有无 PCE 和死亡率的患者之间局部剂量差异进行基于体素的分析（VBA）。基于概率独立成分分析（PICA）和连接图，对 VBA 结果的稳健性进行了新的描述符空间特性的评估。
结果
多变量分析选择了几个非剂量学变量来考虑这些结果，而时间依赖性 PCE 发作与 OS （p=0.34）在多变量 Cox 分析中无关。尽管 PSPT 在剂量学方面有显著优势，但 RT 技术并未影响 PCE 或 OS 的发生。VBA 突出了与心脏和肺部 PCE 终点显著相关的大量重叠簇。未发现与死亡率终点相关的显著剂量学模式。PICA 识别出 43 个均匀分布在胸部内的组件，而连接图显示主要心肺亚结构之间的剂量有适度的相关性。
结论
空间分辨分析强调了与放射性心脏毒性相关的剂量模式，以及在 PSPT 和 IMRT 中观察到的器官基础剂量反应不匹配。事实上，PSPT 避开的胸部区域与 PCE 发展所涉及的区域很少重叠，正如 VBA 所强调的那样。PICA 和连接图被证明是评估 VBA 推断稳健性的有用工具。
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