Inter-observer variability in target delineation increases during adaptive treatment of head-and-neck and lung cancer

<b>Introduction:</b> Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. <b>Material and methods:</b> Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. <b>Results:</b> Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (<i>p</i>-value range .063–.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. <b>Conclusion:</b> IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed.

引言：靶区勾画的观察者间差异（Inter-observer variability, IOV）是放疗领域中已被充分证实的几何不确定性来源。这类差异目前尚未在基于治疗期间获取的影像数据开展适应性重新勾画的场景中得到探索。我们针对局部晚期头颈部鳞状细胞癌（head-and-neck squamous cell carcinoma, HNSCC）以及（非）小细胞肺癌[(non-)small cell lung cancer, (N)SCLC]，对比了治疗前与治疗中期阶段，专家对原发性大体肿瘤靶区（primary gross tumour volume, GTV）与临床靶区（clinical target volume, CTV）的勾画工作中存在的IOV情况。
材料与方法：头颈部鳞癌组与（非）小细胞肺癌组分别有5名和6名观察者参与研究，每组均完成5例病例的靶区勾画。影像数据以CT扫描为基础，部分辅以FDG-PET显像，按治疗前、治疗中期两个独立阶段提供。采用体积重叠指标，即广义符合度指数（Generalised Conformity Index）评估整体勾画兼容性；同时通过计算各观察者勾画结果与中位共识勾画结果之间的表面距离标准差，识别观察者间差异的局部极端值。我们通过问卷调查收集了靶区勾画流程的细节信息，尤其是原发性大体肿瘤靶区向临床靶区的扩边范围以及适应性勾画策略。
结果：体积重叠分析显示，除各瘤种组各1例病例外，其余病例的IOV均出现恶化，但该结果在本次小样本量研究中未达到统计学显著性（p值范围为0.063~0.125）。靶区勾画一致性的变化从原发性大体肿瘤靶区传递至临床靶区，但未得到正式的相关性验证。基于表面距离的分析发现，头颈部鳞癌的靶区纵向范围是普遍存在的意见分歧来源。（非）小细胞肺癌组的高观察者间差异往往与肿瘤毗邻实变肺组织或可能侵犯纵隔有关。观察者间的适应性勾画实践存在较大差异，仅不足半数的观察者表示会在治疗过程中持续沿用治疗前的靶区勾画开展适配调整。
结论：治疗期间靶区勾画的观察者间差异有所增加，而不同机构间适配实践的差异进一步加剧了IOV的传统诱因。目前亟需制定统一的共识指南。