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 ((223)RaCl(2)) for response assessment in osteosarcoma, NAFCIST (Na(18)F PET response Criteria in Solid Tumors). EXPERIMENTAL DESIGN: Patients received one to six cycles of (223)RaCl(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 (Na(18)F) PET was used to characterise the disease. Correlation of biomarkers and survival was analysed with NAFCIST measure from Na(18)F 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 (18)F-FDG PET and Na(18)F 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 Na(18)F PET. Changes in NAFCIST were correlated with changes in bone alkaline phosphatase levels (r=0.54) and negatively with cumulative dose of (223)RaCl(2) (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 Na(18)F 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.