ABSTRACT
Objective:To evaluate the value of pretreatment 18F-fluorodeoxyglucose (FDG) PET/CT-based heterogeneity for early prediction of targeted therapy outcome in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Methods:From May 2012 to April 2018, 29 patients (all females, median age: 52 (32-69) years) who had HER2 positive metastatic breast cancer and underwent pretreatment 18F-FDG PET/CT in Fudan University Shanghai Cancer Center were retrospectively enrolled. All patients received trastuzumab as first-line treatment and were followed up for 6-87 (median time: 35) months. The relations between clinicopathologic parameters or PET/CT-based parameters and progression-free survival (PFS)/overall survival (OS) were analyzed with Cox univariate analysis. The parameters with P≤0.01 were further analyzed with Cox multivariate analysis. Optimal cut-off values were determined by time-dependent receiver operating characteristic (ROC) curve analysis. The survival analyses were estimated by Kaplan-Meier method and log-rank test. Results:The median OS of the 29 patients was 30 (6-83) months, and the median PFS was 10 (2-29) months. The PET/CT-based heterogeneity index(HI), including the maximum standardized uptake value (SUV max) ratio (SUV max-R; hazard ratio ( HR)=8.6, 95% CI: 2.7-27.8, P<0.001), the mean standardized uptake value (SUV mean)-2.5 (the cut-off value of standardized uptake value (SUV)=2.5) ratio (SUV mean-2.5-R; HR=2.6, 95% CI: 1.2-5.9, P=0.020), the metabolic tumor volume(MTV)-2.5 ratio(MTV-2.5-R; HR=2.4, 95% CI: 1.1-5.2, P=0.030), and the total lesion glycolysis(TLG)-2.5 ratio(TLG-2.5-R; HR=3.2, 95% CI: 1.4-7.4, P=0.008) of the lesion with the highest SUV max to that with the lowest SUV max, were significantly associated with PFS. None of the parameters was significantly associated with OS (all P>0.05). Multivariate analysis showed that the SUV max-R was the only independent predictor for PFS ( HR=6.8, 95% CI: 1.8-26.1, P<0.01). Area under the ROC curve for SUV max-R was 0.747. With a cut-off value of 1.8, SUV max-R could effectively distinguish the benefit from non-benefit population treated with trastuzumab (15.0 vs 7.0 months; χ2=18.68, P<0.01). Conclusion:Pretreatment 18F-FDG PET/CT-based HI has potential value for early prediction of first-line trastuzumab treatment outcome in patients with HER2 positive metastatic breast cancer.
ABSTRACT
Background and purpose:In preparation for using this tracer in humans, this study estimated thedosimetry of18F-FES with the method established by MIRD based on whole-body PET imaging of mice.Methods:Three female mice receivedⅣ tail injections of18F-FES and were scanned for 160 min in an Inveon dedicated PET/CT scanner. This study selected some important organs (brain, lung, liver, heart wall, small intestine, large intestine, kidney and urinary bladder), computed their residence times. Then, the residence times in mice organs were converted to human values using scale factors based on differences between organ and body weights. OLINDA/EXM 1.1 software was used to compute the absorbed human doses in multiple organs for both adult female and adult male body phantoms. Results:The highest absorbed doses in gallbladder wall, urinary bladder wall, small intestine, upper large intestine and liver are 0.072 5, 0.044 5, 0.043 0, 0.031 5 and 0.028 2 mGy/MBq, respectively. The organs which have the lowest ab-sorbed doses were brain (0.005 2 mGy/MBq), followed by skin (0.001 1 mGy/MBq), breast (0.001 1 mGy/MBq), heart wall (0.001 2 mGy/MBq) and thyroid (0.001 2 mGy/MBq). The mean absorbed doses for the other major organs ranged from 0.009 5 to 0.023 5 mGy/MBq. The total mean effective dose is 0.019 0 mSv/MBq and the mean effective doses equivalent is 0.025 0 mGy/MBq. A 370-MBq injection of18F-FES leads to an estimated effective dose of 7.03 mSv for the female. There was no statistical difference in the doses results obtained from direct measurement of18F-FES ab-sorption in normal people between previous publications by others and our work.Conclusion:The whole-body mouse imaging can be used as a preclinical tool for initial estimation of the absorbed doses of18F-FES in humans. Furthermore, the potential radiation risk associated with18F-FES imaging is well within the accepted limits.