Department of Experimental Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Cancer Research Program, Research Institute of the McGill University Healthcare Centre, Montreal, Quebec, Canada.
PLoS One. 2023 Apr 13;18(4):e0284282. doi: 10.1371/journal.pone.0284282. eCollection 2023.
Orthotopic non-small cell lung cancer (NSCLC) mice models are important for establishing translatability of in vitro results. However, most orthotopic lung models do not produce localized tumors treatable by conformal radiotherapy (RT). Here we report on the performance of an orthotopic mice model featuring conformal RT treatable tumors following either left or right lung tumor cell implantation. Athymic Nude mice were surgically implanted with H1299 NSCLC cell line in either the left or right lung. Tumor development was tracked bi-weekly using computed tomography (CT) imaging. When lesions reached an appropriate size for treatment, animals were separated into non-treatment (control group) and RT treated groups. Both RT treated left and right lung tumors which were given a single dose of 20 Gy of 225 kV X-rays. Left lung tumors were treated with a two-field parallel opposed plan while right lung tumors were treated with a more conformal four-field plan to assess tumor control. Mice were monitored for 30 days after RT or after tumor reached treatment size for non-treatment animals. Treatment images from the left and right lung tumor were also used to assess the dose distribution for four distinct treatment plans: 1) Two sets of perpendicularly staggered parallel opposed fields, 2) two fields positioned in the anterior-posterior and posterior-anterior configuration, 3) an 180° arc field from 0° to 180° and 4) two parallel opposed fields which cross through the contralateral lung. Tumor volumes and changes throughout the follow-up period were tracked by three different types of quantitative tumor size approximation and tumor volumes derived from contours. Ultimately, our model generated delineable and conformal RT treatable tumor following both left and right lung implantation. Similarly consistent tumor development was noted between left and right models. We were also able to demonstrate that a single 20 Gy dose of 225 kV X-rays applied to either the right or left lung tumor models had similar levels of tumor control resulting in similar adverse outcomes and survival. And finally, three-dimensional tumor approximation featuring volume computed from the measured length across three perpendicular axes gave the best approximation of tumor volume, most closely resembled tumor volumes obtained with contours.
原位非小细胞肺癌（NSCLC）小鼠模型对于建立体外研究结果的转化性非常重要。然而，大多数原位肺模型并不能产生可通过适形放疗（RT）治疗的局部肿瘤。在这里，我们报告了一种新的原位小鼠模型的性能，该模型可通过左侧或右侧肺肿瘤细胞植入产生可通过适形 RT 治疗的肿瘤。无胸腺裸鼠通过手术将 NSCLC 细胞系 H1299 植入左侧或右侧肺。使用计算机断层扫描（CT）成像每两周跟踪一次肿瘤发展情况。当病变达到适合治疗的大小后，将动物分为非治疗（对照组）和 RT 治疗组。对接受 20 Gy 225 kV X 射线单次剂量的左、右肺肿瘤进行 RT 治疗。左侧肺肿瘤采用两野平行对置计划治疗，而右侧肺肿瘤采用更适形的四野计划进行治疗，以评估肿瘤控制情况。在 RT 后或非治疗动物的肿瘤达到治疗大小时，对小鼠进行 30 天监测。还使用来自左、右肺肿瘤的治疗图像评估四种不同治疗计划的剂量分布：1）两组垂直交错的平行对置野，2）一前一后和一后一前配置的两个野，3）从 0°到 180°的 180°弧形野，以及 4）穿过对侧肺的两个平行对置野。通过三种不同类型的定量肿瘤大小近似和从轮廓得出的肿瘤体积，跟踪整个随访期间的肿瘤体积和变化。最终，我们的模型在左侧和右侧肺植入后都产生了可描绘和适形 RT 治疗的肿瘤。左侧和右侧模型之间也观察到了类似的一致肿瘤发展。我们还能够证明，应用于左侧或右侧肺肿瘤模型的单次 20 Gy 225 kV X 射线剂量具有相似的肿瘤控制水平，导致相似的不良后果和生存率。最后，基于三个垂直轴上测量长度计算的三维肿瘤近似给出了肿瘤体积的最佳近似值，与轮廓获得的肿瘤体积最接近。
