Image-guided radiation therapy could benefit from implementing adaptive radiation therapy (ART) techniques. A cycle-generative adversarial network (cycle-GAN)-based cone-beam computed tomography (CBCT)-to-synthetic CT (sCT) conversion algorithm was evaluated regarding image quality, image segmentation and dosimetric accuracy for head and neck (H&N), thoracic and pelvic body regions. Methods: Using a cycle-GAN, three body site-specific models were priorly trained with independent paired CT and CBCT datasets of a kV imaging system (XVI, Elekta). sCT were generated based on first-fraction CBCT for 15 patients of each body region. Mean errors (ME) and mean absolute errors (MAE) were analyzed for the sCT. On the sCT, manually delineated structures were compared to deformed structures from the planning CT (pCT) and evaluated with standard segmentation metrics. Treatment plans were recalculated on sCT. A comparison of clinically relevant dose-volume parameters (D 98 , D 50 and D 2 of the target volume) and 3D-gamma (3%/3mm) analysis were performed. Results: The mean ME and MAE were 1.4, 29.6, 5.4 Hounsfield units (HU) and 77.2, 94.2, 41.8 HU for H&N, thoracic and pelvic region, respectively. Dice similarity coefficients varied between 66.7 ± 8.3% (seminal vesicles) and 94.9 ± 2.0% (lungs). Maximum mean surface distances were 6.3 mm (heart), followed by 3.5 mm (brainstem). The mean dosimetric differences of the target volumes did not exceed 1.7%. Mean 3D gamma pass rates greater than 97.8% were achieved in all cases. Conclusions: The presented method generates sCT images with a quality close to pCT and yielded clinically acceptable dosimetric deviations. Thus, an important prerequisite towards clinical implementation of CBCTbased ART is fulfilled.

Background Daily adaptive radiation therapy (ART) of patients with non-small cell lung cancer (NSCLC) lowers organs at risk exposure while maintaining the planning target volume (PTV) coverage. Thus, ART allows an isotoxic approach with increased doses to the PTV that could improve local tumor control. Herein we evaluate daily online ART strategies regarding their impact on relevant dose-volume metrics. Methods Daily cone-beam CTs (1 × n = 28, 1 × n = 29, 11 × n = 30) of 13 stage III NSCLC patients were converted into synthetic CTs (sCTs). Treatment plans (TPs) were created retrospectively on the first-fraction sCTs (sCT1) and subsequently transferred unaltered to the sCTs of the remaining fractions of each patient (sCT2−n) (IGRT scenario). Two additional TPs were generated on sCT2−n: one minimizing the lung-dose while preserving the D95%(PTV) (isoeffective scenario), the other escalating the D95%(PTV) with a constant V20Gy(lungipsilateral) (isotoxic scenario). Results Compared to the original TPs predicted dose, the median D95%(PTV) in the IGRT scenario decreased by 1.6 Gy ± 4.2 Gy while the V20Gy(lungipsilateral) increased in median by 1.1% ± 4.4%. The isoeffective scenario preserved the PTV coverage and reduced the median V20Gy(lungipsilateral) by 3.1% ± 3.6%. Furthermore, the median V5%(heart) decreased by 2.9% ± 6.4%. With an isotoxic prescription, a median dose-escalation to the gross target volume of 10.0 Gy ± 8.1 Gy without increasing the V20Gy(lungipsilateral) and V5%(heart) was feasible. Conclusions We demonstrated that even without reducing safety margins, ART can reduce lung-doses, while still reaching adequate target coverage or escalate target doses without increasing ipsilateral lung exposure. Clinical benefits by means of toxicity and local control of both strategies should be evaluated in prospective clinical trials.