Imaging acquisition and read procedures
HO location, HO lesions, HO
Whole-body PET–CT scans were acquired. PET–CT acquisition and reconstruction parameters within prespecified ranges were defined for each patient at the baseline scan and kept constant throughout the study. All PET–CT scans were transferred to a contract research organization for centralized quality control and review by two independent readers and an adjudicator; all three were blinded to treatment assignment. Based on preclinical data, we hypothesized that HO lesions which showed the highest uptake of SUVFrom each patient’s baseline PET–CT images, readers selected up to seven candidate active HO pre-existing lesions. Subsequently, an adjudicator chose up to seven lesions from this initial pool as the set of pre-existing lesions to be followed and quantified by both readers, beginning with the lesion with the greatest SUVAppearance of new lesions was assessed by readers post-baseline using PET–CT scans. A third independent blinded reader (the adjudicator) performed forced adjudication when there were discrepancies between the two independent readers in the assessment of new lesions. Readers were blinded to the adjudication. New lesions developing post-baseline as identified by PET were required to be active. New lesions identified by CT alone, consistent with HO location and morphology, were required to have a density >200 HU (well above the value of ~50 HU of soft tissue to increase the certainty of bone identification, but unlikely to exclude cortical HO bone with ~800 HU or greater) with a volume ≥1 cmChanges in volumetric growth were assessed by CT in active, pre-existing lesions. Readers independently assessed PET SUV