PurposeA correct placement of the applicator during intraoperative radiotherapy (IORT) for brain metastasis is of paramount importance, in order to deliver a precise and safe treatment. The applicator-to-surface contact assessment cannot be performed under direct observation, as the applicator itself limits the visual range. No image-guided (IG) verification is currently performed intracranially. We hypothesize that IG-IORT would assure a more precise delivery in the target area. We describe our workflow in a first in-human experience. Methods and MaterialsPhantom-based measurements were performed to reach the best cone-beam computed-tomography (CBCT) imaging quality possible. Once defined, a clinical feasibility study was initiated. An in-room CBCT device is used to acquire intraoperative images after placing the applicator. Repositioning the applicator is thereafter discussed with the surgeon, according to the imaging outcomes, if required. ResultsAn optimal image quality was achieved with 120-kV voltage, 20-mA current and a tube current–time product of 150 mAs. An additional 0.51–mSv patient exposure was calculated for the entire procedure. The wide dynamic range (−600 HU to +600 HU) of CBCT and a 27-HU mean CT values difference between brain tissue and spherical applicator allows distinguishing both structures. In this first in-human experience, the applicator was repositioned after evidencing air gaps, assuring full applicator-to-surface contact. ConclusionThis first in-human procedure confirmed the feasibility of kilovoltage IG-IORT in a neurosurgical setting. A prospective study has been initiated and will provide further dosimetric details.