Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom; Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom.
Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom; Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom.
J Thorac Oncol. 2020 Oct;15(10):1624-1635. doi: 10.1016/j.jtho.2020.06.008. Epub 2020 Jun 14.
Lymphopenia after radiotherapy has an adverse effect on the patient's outcome. However, the relationship between radiotherapy dose delivery and lymphopenia is not fully understood. This work used image-based data mining to identify anatomical regions where the received dose is correlated with severe lymphopenia.
A total of 901 patients with lung cancer were analyzed. A Cox model was used to assess prognostic factors of overall survival (OS). Two matched groups were defined-patients with lymphopenia of grade 3 or higher and patients without lymphopenia of grade 3-based on tumor volume, baseline lymphocytes, and prescribed dose. Then, data mining was used to identify regions where dose correlates significantly with lymphopenia of grade 3 or higher. For this, dose matrices were aligned using registration of the computed tomography images to one reference patient. Mean dose distributions were obtained for the two groups, and organs of significance were detected. Dosimetric parameters from the identified organs that had the highest correlation with lymphocytes at nadir were selected. Multivariable analysis was conducted for lymphopenia of grade 3 or higher on the full lung cohort, and the model was tested on 305 patients with esophageal cancer.
Adjusted Cox regression revealed that lymphopenia of grade 3 or higher is an independent factor of OS. The anatomical regions identified were the heart, lung, and thoracic vertebrae. Dosimetric parameters for lymphopenia included thoracic vertebrae V, mean lung dose, and mean heart dose, which were further validated in the esophageal cancer cohort.
We report that severe lymphopenia during radiotherapy is a poor prognostic factor for OS in patients with lung cancer and could be mitigated by minimizing thoracic vertebrae V, mean lung dose, and mean heart dose to limit the irradiation of stem cells and blood pool.
放疗后出现淋巴细胞减少会对患者的预后产生不利影响。然而，放疗剂量分布与淋巴细胞减少之间的关系尚未完全阐明。本研究采用基于图像的数据挖掘方法，确定与严重淋巴细胞减少相关的受照解剖区域。
共分析了 901 例肺癌患者。采用 Cox 模型评估总生存期（OS）的预后因素。根据肿瘤体积、基线淋巴细胞计数和处方剂量，将淋巴细胞减少 3 级或以上的患者和无淋巴细胞减少 3 级的患者定义为两组匹配。然后，采用数据挖掘方法确定与淋巴细胞减少 3 级或以上相关的剂量区域。为此，使用 CT 图像的配准将剂量矩阵与一个参考患者对齐。为两组获得平均剂量分布，并检测有意义的器官。从与最低点淋巴细胞相关性最高的识别器官中选择具有最高相关性的剂量学参数。对全肺队列进行淋巴细胞减少 3 级或以上的多变量分析，并在 305 例食管癌患者中进行模型测试。
校正后的 Cox 回归显示，淋巴细胞减少 3 级或以上是 OS 的独立预后因素。确定的解剖区域是心脏、肺和胸椎体。与淋巴细胞减少相关的剂量学参数包括胸椎体 V、平均肺剂量和平均心脏剂量，这些参数在食管癌队列中得到进一步验证。
我们报告严重放疗后淋巴细胞减少是肺癌患者 OS 的不良预后因素，可以通过最小化胸椎体 V、平均肺剂量和平均心脏剂量来减轻，从而限制干细胞和血液池的照射。
