本研究旨在调查以4维计算机断层扫描（4DCT）为基础的纵向剂量累积对行标准分数调制放射治疗（IMRT）的局部晚期非小细胞肺癌患者的剂量和临床影响。从随机临床试验中回顾性选择了67名患者。他们的原始IMRT计划、规划和验证的4DCT以及约4个月的治疗后随访CT被导入一个商业化治疗计划系统。应用两种可变形图像配准算法进行剂量累积，并对其准确性进行评估。比较了使用平均灰度图像或相位图像计算的计划和累积剂量。在器官层面上，比较了平均肺剂量和Ⅱ级以上放射性肺炎正常组织并发症概率（NTCP）。在区域层面上，比较了肺亚段的平均剂量和等剂量间重叠的体积。在像素层面上，通过评估剂量与放射学图像密度变化（IDC）模型的拟合度来比较估计的给药剂量的准确性。还比较了根据计划和累积剂量之间NTCP差异（|ΔNTCP|）的大小划分的亚队列的剂量-IDC模型拟合度。可变形图像配准的准确性进行了定量化，并考虑了像素级别的不确定性分析。与计划剂量相比，累积剂量平均增加的肺剂量和NTCP增加均在1 Gy以下和2%以下（最高分别为8.2 Gy和18.8%）。计划和累积剂量分布之间的等剂量间体积重叠范围为0.01至0.93。像素级别的剂量-IDC模型显示了从计划剂量到累积剂量的拟合改善（拟合度伪R2增加0.0023），并且相较于NTCP差异 <2%的患者，NTCP差异 ≥2%的患者的拟合度进一步改善。通过相对较大的队列、强大的图像配准、多层次指标比较以及基于放射学图像的证据，我们证明了剂量累积更准确地表示了给药剂量，并且对于具有更大纵向反应的患者尤其有益。版权所有©2023 Elsevier Inc. 保留所有权利。

The aim of this study was to investigate the dosimetric and clinical effects of 4-dimensional computed tomography (4DCT)-based longitudinal dose accumulation in patients with locally advanced non-small cell lung cancer treated with standard-fractionated intensity-modulated radiation therapy (IMRT).Sixty-seven patients were retrospectively selected from a randomized clinical trial. Their original IMRT plan, planning and verification 4DCTs, and ∼4-month posttreatment follow-up CTs were imported into a commercial treatment planning system. Two deformable image registration algorithms were implemented for dose accumulation, and their accuracies were assessed. The planned and accumulated doses computed using average-intensity images or phase images were compared. At the organ level, mean lung dose and normal-tissue complication probability (NTCP) for grade ≥2 radiation pneumonitis were compared. At the region level, mean dose in lung subsections and the volumetric overlap between isodose intervals were compared. At the voxel level, the accuracy in estimating the delivered dose was compared by evaluating the fit of a dose versus radiographic image density change (IDC) model. The dose-IDC model fit was also compared for subcohorts based on the magnitude of NTCP difference (|ΔNTCP|) between planned and accumulated doses.Deformable image registration accuracy was quantified, and the uncertainty was considered for the voxel-level analysis. Compared with planned doses, accumulated doses on average resulted in <1-Gy lung dose increase and <2% NTCP increase (up to 8.2 Gy and 18.8% for a patient, respectively). Volumetric overlap of isodose intervals between the planned and accumulated dose distributions ranged from 0.01 to 0.93. Voxel-level dose-IDC models demonstrated a fit improvement from planned dose to accumulated dose (pseudo-R2 increased 0.0023) and a further improvement for patients with ≥2% |ΔNTCP| versus for patients with <2% |ΔNTCP|.With a relatively large cohort, robust image registrations, multilevel metric comparisons, and radiographic image-based evidence, we demonstrated that dose accumulation more accurately represents the delivered dose and can be especially beneficial for patients with greater longitudinal response.Copyright © 2023 Elsevier Inc. All rights reserved.