Department of Radiation Oncology, School of Medicine and Klinikum rechts der Isar, Technical University of Munich (TUM), 81675, Munich, Germany.
Institute of Radiation Medicine (IRM), Helmholtz Zentrum München (HMGU) GmbH German Research Center for Environmental Health, 85764, Neuherberg, Germany.
Radiat Oncol. 2024 Nov 22;19(1):169. doi: 10.1186/s13014-024-02561-z.
Post-Therapy-Pneumonitis (PTP) is a critical side effect of both, thoracic radio(chemo)therapy (R(C)T) and immune checkpoint inhibition (ICI). However, disease characteristics and patient-specific risk factors of PTP after combined R(C)T + ICI are less understood. Given that RT-triggered PTP is strongly dependent on the volume and dose of RT [1], driven by inflammatory mechanisms, we hypothesize that combination therapy of R(C)T with ICI influences the dose-volume-effect correlation for PTP. This study focuses on the development of a method for evaluation of alterations of dosimetric parameters for PTP after R(C)T with and without ICI.
PTP volumes were delineated on the follow-up diagnostic Computed Tomography (CT) and deformably matched to the planning CT for patients with PTP after thoracic R(C)T + ICI or R(C)T. Dose data was converted to 2-Gy equivalent doses (EQD2) and dosimetrically analyzed. Dosimetric and volumetric parameters of the segmented PTP volumes were analyzed. The method was exemplarily tested on an internal patient cohort including 90 patients having received thoracic R(C)T + ICI (39) and R(C)T (51). Thirtytwo patients with PTP were identified for further analysis. Additional data on previous chemotherapy, RT, smoking status and pulmonary co-morbidity were conducted. A matched pair analysis with regard to planning target volumes (PTV) was conducted for curative intended (definitive) and palliative patient cohorts individually.
The presented method was able to quantify and compare the dosimetric parameters of PTP for the different therapies. For our study group, no significant differences between R(C)T + ICI and R(C)T only was observed. However, the dosimetric analysis revealed large volumetric fractions (55%) of the PTP volumes to be located outside of high dose (EQD2 < 40 Gy) regions for R(C)T + ICI. There was a non-significant trend towards increased area under the curve of the dose volume histogram (AUC) values for R(C)T + ICI compared to R(C)T only (3743.6 Gy∙% vs. 2848.8 Gy∙%; p-value = 0.171). In contrast to the data for the palliative intended treatment group, for definitive R(C)T + ICI, data tended towards increased volumes with higher doses.
The proposed method was capable to quantify dosimetric differences in the dose-volume-effect relationship of PTP for patients with R(C)T + ICI and patients with R(C)T only. In this exploratory analysis, no significant dosimetric differences within PTP volumes for the different groups could be observed. However, our observations suggest, that for safe application of thoracic R(C)T + ICI, further careful investigation of dosimetric prescription and analysis concepts with larger and conformer study groups is recommendable.
放射性治疗后肺炎（PTP）是胸部放射治疗（RT）联合放化疗（RCT）和免疫检查点抑制（ICI）的一种严重的副作用。然而，联合 RCT+ICI 后 PTP 的疾病特征和患者特定的危险因素尚不清楚。鉴于 RT 引发的 PTP 强烈依赖于 RT 的体积和剂量[1]，受炎症机制驱动，我们假设 RCT 联合 ICI 的治疗会影响 PTP 的剂量-体积效应相关性。本研究的重点是开发一种方法，用于评估接受 RCT+ICI 和 RCT 后 PTP 的剂量学参数的变化。
在接受 RCT+ICI 或 RCT 后的随访诊断 CT 上对 PTP 进行勾画，并对 PTP 进行变形配准到计划 CT。将剂量数据转换为 2-Gy 等效剂量（EQD2）并进行剂量学分析。对分段 PTP 体积的剂量学和体积参数进行分析。该方法通过一个内部患者队列进行了实例测试，该队列包括 90 名接受了胸部 RCT+ICI（39 名）和 RCT（51 名）的患者。对 32 名患有 PTP 的患者进行了进一步分析。对以前的化疗、RT、吸烟状况和肺部合并症进行了额外的数据收集。对接受根治性（确定性）和姑息性治疗的患者队列分别进行了计划靶区（PTV）的配对分析。
所提出的方法能够定量和比较不同治疗方法的 PTP 的剂量学参数。对于我们的研究组，RCT+ICI 和仅 RCT 之间没有观察到显著差异。然而，剂量学分析显示，RCT+ICI 的 PTP 体积中有很大的体积分数（55%）位于高剂量（EQD2<40 Gy）区域之外。与仅接受 RCT 相比，RCT+ICI 的剂量-体积直方图（AUC）值的曲线下面积（AUC）值有增加的趋势（3743.6 Gy·%比 2848.8 Gy·%；p 值=0.171）。与姑息性治疗组的数据相反，对于确定性 RCT+ICI，高剂量的 PTP 体积有增加的趋势。
所提出的方法能够定量比较接受 RCT+ICI 和仅接受 RCT 的患者的 PTP 的剂量-体积效应关系中的剂量学差异。在这项探索性分析中，不同组之间的 PTP 体积内没有观察到显著的剂量学差异。然而，我们的观察结果表明，为了安全应用胸部 RCT+ICI，需要进一步仔细研究剂量学处方和分析概念，并使用更大的、更一致的研究组进行研究。
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