This work evaluated the use of the positron emission tomography (PET)/computed tomography (CT) technique to assess the early therapeutic response and predict the prognosis of patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) who underwent apatinib therapy. Standardised uptake value (SUV), metabolic tumour volume (MTV) and total lesion glycolysis (TLG), derived from 18F-FDG PET/CT and SUV from 68Ga-NOTA-PRGD2 PET/CT were evaluated. Tumour response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Sixteen of 20 patients achieved partial response (PR) and four of 20 had stable disease (SD) after apatinib therapy. Six progression-free survival (PFS) events occurred. A strong correlation was observed between the best change in the sum of the longest diameters of target lesions (ΔCT%) and 18F-FDG PET/CT indices after the completion of the first treatment cycle (ΔMTV% (P = 0.0019), ΔTLG% (P = 0.0021) and ΔSUVmax% (P = 0.0443)). A significant difference in PFS was observed between patients with ΔMTV% <−45% and ≥−45% (P = 0.0019) and between patients with ΔTLG% <−80% and ≥−80% (P = 0.0065). Ten of 11 patients presented a decrease in SUVmax on 68Ga-NOTA-PRGD2 PET/CT after two cycles of apatinib therapy and showed PR, whereas one patient presenting an increase in SUVmax only showed SD as the best response. When a cut-off value of the target/background ratio at −20% was used, two PFS curves showed a significant difference (P = 0.0016). Hence, early assessment by 18F-FDG and 68Ga-NOTA-PRGD2 PET/CT was effective in the prediction and evaluation of RAIR-DTC treated with apatinib.
Chen Wang, Xin Zhang, Xue Yang, Hui Li, Ruixue Cui, Wenmin Guan, Xin Li, Zhaohui Zhu and Yansong Lin
James F Powers, Brent Cochran, James D Baleja, Hadley D Sikes, Xue Zhang, Inna Lomakin, Troy Langford, Kassi Taylor Stein and Arthur S Tischler
We describe a unique patient-derived xenograft (PDX) and cell culture model of succinate dehydrogenase-deficient gastrointestinal stromal tumor (SDH-deficient GIST), a rare mesenchymal tumor that can occur in association with paragangliomas in hereditary and non-hereditary syndromes. This model is potentially important for what it might reveal specifically pertinent to this rare tumor type and, more broadly, to other types of SDH-deficient tumors. The primary tumor and xenografts show a very high proliferative fraction, and distinctive morphology characterized by tiny cells with marked autophagic activity. It is likely that these characteristics resulted from the combination of the germline SDHB mutation and a somatic KRAS G12D mutation. The most broadly relevant findings to date concern oxygen and oxidative stress. In paragangliomas harboring SDHx mutations, both hypoxic signaling and oxidative stress are putative drivers of tumor growth. However, there are no models for SDH-deficient paragangliomas. This related model is the first from a SDHB-mutated human tumor that can be experimentally manipulated to study mechanisms of oxygen effects and novel treatment strategies. Our data suggest that tumor growth and survival require a balance between protective effects of hypoxic signaling vs deleterious effects of oxidative stress. While reduced oxygen concentration promotes tumor cell survival, a further survival benefit is achieved with antioxidants. This suggests potential use of drugs that increase oxidative stress as novel therapies. In addition, autophagy, which has not been reported as a major finding in any type of SDH-deficient tumor, is a potential target of agents that might trigger autophagic cell death.