Abstract
Accurate tumor delineation is foundational to radiotherapy. In the era of deep learning, the automation of this labor-intensive and variation-prone process is increasingly tractable. We developed a deep neural network model to segment gross tumor volumes (GTVs) in the lung and propagate them across 4D CT images to generate an internal target volume (ITV), capturing tumor motion during respiration. Using a multicenter cohort-based registry from 9 clinics across 2 health systems, we trained a 3D UNet model (iSeg) on pre-treatment CT images and corresponding GTV masks (n = 739, 5-fold cross-validation) and validated it on two independent cohorts (n = 161; n = 102). The internal cohort achieved a median Dice (DSC) of 0.73 [IQR: 0.62-0.80], with comparable performance in external cohorts (DSC = 0.70 [0.52-0.78] and 0.71 [0.59-79]), indicating multi-site validation. iSeg matched human inter-observer variability and was robust to image quality and tumor motion (DSC = 0.77 [0.68-0.86]). Machine-generated ITVs were significantly smaller than physician delineated contours (p < 0.0001), indicating more precise delineation. Notably, higher false positive voxel rate (regions segmented by the machine but not the human) were associated with increased local failure (HR: 1.01 per voxel, p = 0.03), suggesting the clinical relevance of these discordant regions. These results mark a leap in automated target volume segmentation and suggest that machine delineation can enhance the accuracy, reproducibility, and efficiency of this core task in radiotherapy.