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 (223RaCl2) for response assessment in osteosarcoma, NAFCIST (Na18F PET response Criteria in Solid Tumors).
Experimental design Patients received one to six cycles of 223RaCl2, and cumulative doses varied from 6.84 MBq to 57.81 MBq. Molecular imaging with technetium-99m phosphonate scintigraphy, fluorine-18-fluorodeoxyglucose (18FDG) positron emission tomography (PET) or sodium fluoride-18 (Na18F) PET was used to characterise the disease. Correlation of biomarkers and survival was analysed with NAFCIST measure from Na18F 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 18F-FDG PET and Na18F 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 Na18F PET. Changes in NAFCIST were correlated with changes in bone alkaline phosphatase levels (r=0.54) and negatively with cumulative dose of 223RaCl2 (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 Na18F 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.
- Na18F PET
- 18F-FDG PET
- bone scintigraphy
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Contributors KK, VS: conception, study design, provision of study materials, wrote the first draft, analysed the data, revised reviewer comments. ER, PMA, GR, HAM: conception, study design, critical revision of paper. AR: biostatistical analysis and critical revision of the paper.
Funding Funding was provided by the Shannon Wilkes osteosarcoma research programme, the High-Impact Clinical Research Support Program (HI-CRSP) at The University of Texas MD Anderson Cancer Center, and the National Institutes of Health Cancer Center Support Grant CA016672.
Competing interests Vivek Subbiah receives research funding forclinical trials from Novartis, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth,Incyte, Fujifilm, Pharmamar, D3, Pfizer, Multivir, Amgen, Abbvie, Alfa-sigma,Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprintmedicines, Loxo oncology, Takeda and Roche/ Genentech, National ComprehensiveCancer Network, NCI-CTEP and UT MD Anderson Cancer Center. Travel: Novartis, Pharmamar, AstraZeneca/Medimmune
Patient consent for publication Not required.
Ethics approval The UT MD Anderson Cancer Center Institutional Review Board approved the protocol.
Provenance and peer review Not commissioned; externally peer reviewed.
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