The use of deep learning (DL) to improve cone‐beam CT (CBCT) image quality has gained popularity as computational resources and algorithmic sophistication have advanced in tandem. CBCT imaging has the potential to facilitate online adaptive radiation therapy (ART) by utilizing up‐to‐date patient anatomy to modify treatment parameters before irradiation. Poor CBCT image quality has been an impediment to realizing ART due to the increased scatter conditions inherent to cone‐beam acquisitions. Given the recent interest in DL applications in radiation oncology, and specifically DL for CBCT correction, we provide a systematic theoretical and literature review for future stakeholders. The review encompasses DL approaches for synthetic CT generation, as well as projection domain methods employed in the CBCT correction literature. We review trends pertaining to publications from January 2018 to April 2022 and condense their major findings—with emphasis on study design and DL techniques. Clinically relevant endpoints relating to image quality and dosimetric accuracy are summarized, highlighting gaps in the literature. Finally, we make recommendations for both clinicians and DL practitioners based on literature trends and the current DL state‐of‐the‐art methods utilized in radiation oncology.

Purpose: This study aimed to develop and assess an automated segmentation framework based on deep learning for metastatic prostate cancer (mPCa) lesions in whole-body [⁶⁸Ga]Ga-PSMA-11 PET/CT images for the purpose of extracting patient-level prognostic biomarkers. Methods: Three hundred thirty-seven [⁶⁸Ga]Ga-PSMA-11 PET/CT images were retrieved from a cohort of biochemically recurrent PCa patients. A fully 3D convolutional neural network (CNN) is proposed which is based on the self-configuring nnU-Net framework, and was trained on a subset of these scans, with an independent test set reserved for model evaluation. Voxel-level segmentation results were assessed using the dice similarity coefficient (DSC), positive predictive value (PPV), and sensitivity. Sensitivity and PPV were calculated to assess lesion level detection; patient-level classification results were assessed by the accuracy, PPV, and sensitivity. Whole-body biomarkers total lesional volume (TLV_auto) and total lesional uptake (TLU_auto) were calculated from the automated segmentations, and Kaplan–Meier analysis was used to assess biomarker relationship with patient overall survival. Results: At the patient level, the accuracy, sensitivity, and PPV were all > 90%, with the best metric being the PPV (97.2%). PPV and sensitivity at the lesion level were 88.2% and 73.0%, respectively. DSC and PPV measured at the voxel level performed within measured inter-observer variability (DSC, median = 50.7% vs. second observer = 32%, p = 0.012; PPV, median = 64.9% vs. second observer = 25.7%, p < 0.005). Kaplan–Meier analysis of TLV_auto and TLU_auto showed they were significantly associated with patient overall survival (both p < 0.005). Conclusion: The fully automated assessment of whole-body [⁶⁸Ga]Ga-PSMA-11 PET/CT images using deep learning shows significant promise, yielding accurate scan classification, voxel-level segmentations within inter-observer variability, and potentially clinically useful prognostic biomarkers associated with patient overall survival. Trial registration: This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000608561) on 11 June 2015.