Development of sodium fluoride PET response criteria for solid tumours (NAFCIST) in a clinical trial of radium-223 in osteosarcoma: from RECIST to PERCIST to NAFCIST

Purpose The development of osteosarcoma therapeutics has been challenging, in part because of the lack of appropriate criteria to evaluate responses. We developed a novel criteria in a clinical trial of radium-223 dichloride ((RaCl2)-Ra-223) for response assessment in osteosarcoma, NAFCIST ((NaF)-F-18 PET response Criteria in Solid Tumors). Experimental design Patients received one to six cycles of 223RaCl(2), and cumulative doses varied from 6.84 MBq to 57.81 MBq. Molecular imaging with technetium-99m phosphonate scintigraphy, fluorine-18-fluorodeoxyglucose ((18)FDG) positron emission tomography (PET) or sodium fluoride-18 ((NaF)-F-18) PET was used to characterise the disease. Correlation of biomarkers and survival was analysed with NAFCIST measure from (NaF)-F-18 PET. Results Of the 18 patients, 17 had bone lesions visible in at least one of the imaging studies. In four of seven patients with multiple skeletal lesions (> 5), FDG PET and NaF PET studies could be compared. The skeletal tumour locations varied in our patient population: cranium=2, extremities=7, pelvis=10, spine=12 and thorax=9. The F-18-FDG PET and (NaF)-F-18 PET studies could be compared in all four patients who had multiple lung lesions (>5). Overall the Response Evaluation Criteria in Solid Tumors response was seen in one patient, but four patients experienced mixed responses better defined by (NaF)-F-18 PET. Changes in NAFCIST were correlated with changes in bone alkaline phosphatase levels (r=0.54) and negatively with cumulative dose of (RaCl2)-Ra-223 (r=-0.53). NAFCIST correlated with overall survival (p value of 0.037) while the PERCIST (PET Response Criteria in Solid Tumors) did not (p value of 0.19). Conclusions Our results indicate that (NaF)-F-18 PET should be further studied in osteosarcoma staging. NAFCIST may be a promising criteria for high-risk osteosarcoma response evaluation and correlates with survival. Further validation studies are needed.