Dataset Information

Prospective study of serial 18F-FDG PET and 18F-fluoride (18F-NaF) PET to predict time to skeletal related events, time-to-progression, and survival in patients with bone-dominant metastatic breast cancer.

ABSTRACT: Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18F-FDG PET was predictive of time to skeletal related events (tSRE) and time-to-progression (TTP). 18F-NaF PET improves bone metastasis detection compared to bone scans. We prospectively tested 18F-FDG PET and 18F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (BD MBC). Methods: Patients with BD MBC were imaged with 18F-FDG PET and 18F-NaF PET prior to starting new therapy (scan1) and again at a range of times centered around approximately 4 months later (scan2). SUVmax and SULpeak were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and 18F-FDG PET and 18F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) criteria were also applied. Survival curves for mPERCIST compared response categories of Complete Response+Partial Response+Stable Disease versus Progressive Disease (CR+PR+SD vs PD) for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher FDG SULpeak at scan2 predicted shorter time to tSRE (P = <0.001) and TTP (P = 0.044). Higher FDG SUVmax at scan2 predicted a shorter time to tSRE (P = <0.001). A multivariable model using FDG SUVmax of the index lesion at scan1 plus the difference in SUVmax of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by 18F-FDG PET mPERCIST, tSRE and TTP were longer in responders (CR, PR, or stable) compared to non-responders (PD) (P = 0.007, 0.028 respectively), with a trend toward improved survival (P = 0.1). An increase in the uptake between scans of up to 5 lesions by 18F-NaF PET was associated with longer OS (P = 0.027). Conclusion: Changes in 18F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial 18F-NaF PET was associated with OS, but was not useful for predicting TTP or tSRE in BD MBC.

SUBMITTER: Peterson LM

PROVIDER: S-EPMC6278903 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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Prospective Study of Serial 18F-FDG PET and 18F-Fluoride PET to Predict Time to Skeletal-Related Events, Time to Progression, and Survival in Patients with Bone-Dominant Metastatic Breast Cancer.

Peterson Lanell M LM O'Sullivan Janet J Wu Qian Vicky QV Novakova-Jiresova Alena A Jenkins Isaac I Lee Jean H JH Shields Andrew A Montgomery Susan S Linden Hannah M HM Gralow Julie J Gadi Vijayakrishna K VK Muzi Mark M Kinahan Paul P Mankoff David D Specht Jennifer M JM

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20180510 12

Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18F-FDG PET was predictive of time to skeletal-related events (tSRE) and time to progression (TTP). 18F-NaF PET improves bone metastasis detection compared with bone scanning. We prospectively tested 18F-FDG PET and 18F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (MBC). Metho ...[more]

PMID: 29748233

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Project description:18F-NaF, a PET radiotracer of bone turnover, has shown potential as an imaging biomarker for assessing the response of bone metastases to therapy. This study aimed to evaluate the repeatability of 18F-NaF PET-derived SUV imaging metrics in individual bone lesions from patients in a multicenter study.MethodsThirty-five castration-resistant prostate cancer patients with multiple metastases underwent 2 whole-body (test-retest) 18F-NaF PET/CT scans 3 ± 2 d apart from 1 of 3 imaging sites. A total of 411 bone lesions larger than 1.5 cm3 were automatically segmented using an SUV threshold of 15 g/mL. Two levels of analysis were performed: lesion-level, in which measures were extracted from individual-lesion regions of interest (ROI), and patient-level, in which all lesions within a patient were grouped into a patient ROI for analysis. Uptake was quantified with SUVmax, SUVmean, and SUVtotal Test-retest repeatability was assessed using Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation, critical percentage difference, and repeatability coefficient. The 95% limit of agreement (LOA) of the ratio between test and retest measurements was calculated.ResultsAt the lesion level, the coefficient of variation for SUVmax, SUVmean, and SUVtotal was 14.1%, 6.6%, and 25.5%, respectively. At the patient level, it was slightly smaller: 12.0%, 5.3%, and 18.5%, respectively. ICC was excellent (>0.95) for all SUV metrics. Lesion-level 95% LOA for SUVmax, SUVmean, and SUVtotal was (0.76, 1.32), (0.88, 1.14), and (0.63, 1.71), respectively. Patient-level 95% LOA was slightly narrower, at (0.79, 1.26), (0.89, 1.10), and (0.70, 1.44), respectively. We observed significant differences in the variance and sample mean of lesion-level and patient-level measurements between imaging sites.ConclusionThe repeatability of SUVmax, SUVmean, and SUVtotal for 18F-NaF PET/CT was similar between lesion- and patient-level ROIs. We found significant differences in lesion-level and patient-level distributions between sites. These results can be used to establish 18F-NaF PET-based criteria for assessing treatment response at the lesion and patient levels. 18F-NaF PET demonstrates repeatability levels useful for clinically quantifying the response of bone lesions to therapy.

Project description:BackgroundAssessment of dual time point (DTP) positron emission tomography was carried out with the aim of a quantitative determination of Km, the metabolic uptake rate of [18F]fluorodeoxyglucose as a measure of glucose consumption.MethodsStarting from the Patlak equation, it is shown that Km?mt/ca0+V?r/?a, where mt is the secant slope of the tissue response function between the dual time point measurements centered at t?=?t0. ca0=ca(t0) denotes arterial tracer concentration, V?r is an estimate of the Patlak intercept, and ?a is the time constant of the ca(t) decrease. We compared the theoretical predictions with the observed relation between Ks=mt/ca0 and Km in a group of nine patients with liver metastases of colorectal cancer for which dynamic scans were available, and Km was derived from conventional Patlak analysis. Twenty-two lesion regions of interest (ROIs) were evaluated. ca(t) was determined from a three-dimensional ROI in the aorta. Furthermore, the correlation between Km and late standard uptake value (SUV) as well as retention index was investigated. Additionally, feasibility of the approach was demonstrated in a whole-body investigation.ResultsPatlak analysis yielded a mean Vr of V?r=0.53±0.08 ml/ml. The patient averaged ?a was 99?±?23 min. Linear regression between Patlak-derived Km and DTP-derived Ks according to Ks?=?b?·?Km?+?a yielded b?=?0.98?±?0.05 and a?=?-0.0054?±?0.0013 ml/min/ml (r?=?0.98) in full accordance with the theoretical predictions b?=?1 and a?-V?r/?a. Ks exhibits better correlation with Km than late SUV and retention index, respectively. Ks(c)=Ks+V?r/?a is proposed as a quantitative estimator of Km which is independent of patient weight, scan time, and scanner calibration.ConclusionQuantification of Km from dual time point measurements compatible with clinical routine is feasible. The proposed approach eliminates the issues of static SUV and conventional DTP imaging regarding influence of chosen scanning times and inter-study variability of the input function. Ks and Ks(c) exhibit improved stability and better correlation with the true Km. These properties might prove especially relevant in the context of radiation treatment planning and therapy response control.

Project description:We extracted image features from serial 18F-labeled fluorodeoxyglucose (FDG) positron emission tomography (PET) / computed tomography (CT) scans of anal cancer patients for the prediction of tumor recurrence after chemoradiation therapy (CRT). Seventeen patients (4 recurrent and 13 non-recurrent) underwent three PET/CT scans at baseline (Pre-CRT), in the middle of the treatment (Mid-CRT) and post-treatment (Post-CRT) were included. For each patient, Mid-CRT and Post-CRT scans were aligned to Pre-CRT scan. Comprehensive image features were extracted from CT and PET (SUV) images within manually delineated gross tumor volume, including geometry features, intensity features and texture features. The difference of feature values between two time points were also computed and analyzed. We employed univariate logistic regression model, multivariate model, and naïve Bayesian classifier to analyze the image features and identify useful tumor recurrent predictors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of the prediction. In univariate analysis, six geometry, three intensity, and six texture features were identified as significant predictors of tumor recurrence. A geometry feature of Roundness between Post-CRT and Pre-CRT CTs was identified as the most important predictor with an AUC value of 1.00 by multivariate logistic regression model. The difference of Number of Pixels on Border (geometry feature) between Post-CRT and Pre-CRT SUVs and Elongation (geometry feature) of Post-CRT CT were identified as the most useful feature set (AUC = 1.00) by naïve Bayesian classifier. To investigate the early prediction ability, we used features only from Pre-CRT and Mid-CRT scans. Orientation (geometry feature) of Pre-CRT SUV, Mean (intensity feature) of Pre-CRT CT, and Mean of Long Run High Gray Level Emphasis (LRHGLE) (texture feature) of Pre-CRT CT were identified as the most important feature set (AUC = 1.00) by multivariate logistic regression model. Standard deviation (intensity feature) of Mid-CRT SUV and difference of Mean of LRHGLE (texture feature) between Mid-CRT and Pre-CRT SUVs were identified as the most important feature set (AUC = 0.86) by naïve Bayesian classifier. The experimental results demonstrated the potential of serial PET/CT scans in early prediction of anal tumor recurrence.

Project description:Aortic valve calcification is a slow and progressive pathological process that can manifest in various degrees from mild thickening of the valve known as aortic sclerosis to severe calcification that hinders the leaflet motion, known as aortic stenosis. The evolving concept of aortic calcification is thought to result from infiltration of macrophages and T-lymphocytes. Moreover, the incidence of aortic valve calcification increases with age, in particular over the age of 50. In this study, we aimed to assess 18F-sodium fluoride (18F-NaF) uptake by the aortic valve on PET/CT scans performed in two age groups; 25-35 and 50-75 years of age. We hypothesized that patients aged 50-75, comprising of both healthy and high risk for cardiovascular disease (CVD), would have higher uptake of 18F-NaF than patients aged 25-35 and further that in the former group those who were at high risk for CVD had also higher 18F-NaF uptake. The 25-35-year group comprised of 6 males and 6 females, mean age 30 ± 3.5 years, while the 50-75-year group included 18 males and 20 females, mean age 61 ± 6.2 years. All underwent PET/CT imaging 90 minutes following the injection of 2.2 MBq of 18F-NaF per kg body weight. Aortic valve analysis was performed on axial sections using standard guided computer software (OsiriX MD software, version 9.0.02). The average aortic valve SUVmean was calculated for each patient. Univariate regression models stratified by age group were employed to determine the association of SUVmean with age. In the 50-75-year group, explanatory multivariable regression modeling was applied using available demographic and baseline information. SUVmean was found to be higher in the 50-75 age group than in the 25-35 age group: 0.91 ± 0.25 and 0.86 ± 0.26, respectively. The association of SUVmean with age was much stronger in individuals aged 50-75 years (r = 0.64, P<0.001) than individuals aged 25-35 years (r = 0.20, P = 0.53). In addition, in the 50-75 age group the association was much stronger in subjects with a high risk of CVD than in individuals without: r = 0.68, P = 0.001 versus r = 0.48, P = 0.042. Furthermore, the SUVmean was found to be higher in the high-risk group aged 50-75 than in the low-risk healthy group aged 50-75: 0.98 ± 0.32 and 0.83 ± 0.13. Aortic valve 18F-NaF uptake was higher in patients belonging to the age group of 50-75 years and correlated positively with age and high risk of CVD. These data provide evidence for a potential role of 18F-NaF PET/CT in identifying calcific changes in the aortic valve and may help direct therapeutic intervention prior to the development of symptomatic valvular disease.

Dataset Information

Prospective study of serial 18F-FDG PET and 18F-fluoride (18F-NaF) PET to predict time to skeletal related events, time-to-progression, and survival in patients with bone-dominant metastatic breast cancer.

Publications

Prospective Study of Serial <sup>18</sup>F-FDG PET and <sup>18</sup>F-Fluoride PET to Predict Time to Skeletal-Related Events, Time to Progression, and Survival in Patients with Bone-Dominant Metastatic Breast Cancer.

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