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To determine the most suitable lesion size and depth for radiotherapy treatments with a prototype kilovoltage x-ray arc therapy (KVAT) system through Monte Carlo simulations of the dose delivered to lesion, dose homogeneity, and lesion-to-skin ratio.Monte Carlo simulations were used to calculate dose distributions generated by a novel low-energy kilovoltage x-ray system to a variety of clinically relevant lesion sizes and depths in phantoms and for hypothetical partial breast irradiations of patients in supine and prone positions. The treatments by 200 kV KVAT system were modeled for four sizes of tumor (1–4 cm diameter) at three depths (superficial, middle, and deep) in two sizes of cylindrical water phantoms (16.2-cm and 32.2-cm diameter). In addition, treatments of 3-cm and 4-cm diameter lesions were modeled for two breast patients in prone and supine positions. Dose distributions were calculated using the EGSnrc/DOSXYZnrc code package. Phantom study metrics included lesion-to-skin ratio, dose delivered to isocenter (cGy/min), dose homogeneity, dose profiles, and cumulative dose volume histograms. Lesion-to-skin ratio, lesion-to-rib ratio, dose profiles, and cumulative dose volume histograms were used to evaluate simulated breast patient treatments. Supine breast irradiations were compared to 6-MV VMAT plans. The criterion applied to evaluate the dose distributions was derived from NSABP-B39/RTOG 0413 for accelerated partial breast irradiation. Skin dose was limited to a maximum of 250 cGy for a prescribed lesion dose of 385 cGy per fraction (with the whole treatment being delivered in 10 fractions). This produced the minimum lesion-to-skin dose ratio of 1.5 that served as the main guideline, along with other metrics, for evaluation of future clinical viability of treatments.Phantom dose distributions in the centrally located lesions treated with 360-degree KVAT were found to be superior to dose distributions in off-center lesions with the exception of isocenter dose, which was highest for lesions located closer to the phantom surface. Dose metrics were more favorable for smaller lesions, suggesting that KVAT might be most suitable for treatment of lesions of 1–2 cm in diameter down to depths of 8.1 cm along with 3 cm lesions at depths from 3 cm to 8.1 cm. In addition, treatments of 4-cm lesions were found to be acceptable down to the depths of 4.1 cm (in the 16.2-cm phantom) and 8.1 cm (in the 32.2-cm phantom). At depths from 8.1-cm to 16.1-cm, treatments of 1-cm to 4-cm lesions are possible at the cost of decreased dose rate. KVAT breast treatments in the supine patient position demonstrated that increasing the arc angle and decreasing lesion size improved lesion-to-skin ratio and lesion-to-rib ratio. Supine breast data indicate that 3-cm lesions are treatable at a minimum depth of 3 cm. The 6-MV VMAT plan resulted in lower doses to the ipsilateral lung and the body, but a higher heart dose compared to the KVAT plans. Dose distributions for the prone breast phantoms were superior to the supine cases due to the increased treatment angle of 360-degrees.Although nonoptimized KVAT dose distributions presented here were of inferior quality to VMAT plans, this work has demonstrated the feasibility of delivering low-energy kilovoltage x-rays to lesions up to 4 cm in diameter to depths of 8.1 cm while sparing surrounding tissue.