There is increased interest in various new quantitative uptake metrics beyond SUV in oncologic PET/CT studies. The purpose of this study was to investigate the variability and test–retest ratio (TRT) of metabolically active tumor volume (MATV) measurements and several other new quantitative metrics in non–small cell lung cancer using 18F-FDG PET/CT with different segmentation methods, user interactions, uptake intervals, and reconstruction protocols. Methods: Ten patients with advanced non–small cell lung cancer received 2 series of 2 whole-body 18F-FDG PET/CT scans at 60 min after injection and at 90 min after injection. PET data were reconstructed with 4 different protocols. Eight segmentation methods were applied to delineate lesions with and without a tumor mask. MATV, SUVmax, SUVmean, total lesion glycolysis, and intralesional heterogeneity features were derived. Variability and repeatability were evaluated using a generalized-estimating-equation statistical model with Bonferroni adjustment for multiple comparisons. The statistical model, including interaction between uptake interval and reconstruction protocol, was applied individually to the data obtained from each segmentation method. Results: Without masking, none of the segmentation methods could delineate all lesions correctly. MATV was affected by both uptake interval and reconstruction settings for most segmentation methods. Similar observations were obtained for the uptake metrics SUVmax, SUVmean, total lesion glycolysis, homogeneity, entropy, and zone percentage. No effect of uptake interval was observed on TRT metrics, whereas the reconstruction protocol affected the TRT of SUVmax. Overall, segmentation methods showing poor quantitative performance in one condition showed better performance in other (combined) conditions. For some metrics, a clear statistical interaction was found between the segmentation method and both uptake interval and reconstruction protocol. Conclusion: All segmentation results need to be reviewed critically. MATV and other quantitative uptake metrics, as well as their TRT, depend on segmentation method, uptake interval, and reconstruction protocol. To obtain quantitative reliable metrics, with good TRT performance, the optimal segmentation method depends on local imaging procedure, the PET/CT system, or reconstruction protocol. Rigid harmonization of imaging procedure and PET/CT performance will be helpful in mitigating this variability.
Change in (18)F-FDG uptake may predict response to anticancer treatment. The PERCIST suggest a threshold of 30% change in SUV to define partial response and progressive disease. Evidence underlying these thresholds consists of mixed stand-alone PET and PET/CT data with variable uptake intervals and no consensus on the number of lesions to be assessed. Additionally, there is increasing interest in alternative (18)F-FDG uptake measures such as metabolically active tumor volume and total lesion glycolysis (TLG). The aim of this study was to comprehensively investigate the repeatability of various quantitative whole-body (18)F-FDG metrics in non-small cell lung cancer (NSCLC) patients as a function of tracer uptake interval and lesion selection strategies.Eleven NSCLC patients, with at least 1 intrathoracic lesion 3 cm or greater, underwent double baseline whole-body (18)F-FDG PET/CT scans at 60 and 90 min after injection within 3 d. All (18)F-FDG-avid tumors were delineated with an 50% threshold of SUVpeak adapted for local background. SUVmax, SUVmean, SUVpeak, TLG, metabolically active tumor volume, and tumor-to-blood and -liver ratios were evaluated, as well as the influence of lesion selection and 2 methods for correction of uptake time differences.The best repeatability was found using the SUV metrics of the averaged PERCIST target lesions (repeatability coefficients < 10%). The correlation between test and retest scans was strong for all uptake measures at either uptake interval (intraclass correlation coefficient > 0.97 and R(2) > 0.98). There were no significant differences in repeatability between data obtained 60 and 90 min after injection. When only PERCIST-defined target lesions were included (n = 34), repeatability improved for all uptake values. Normalization to liver or blood uptake or glucose correction did not improve repeatability. However, after correction for uptake time the correlation of SUV measures and TLG between the 60- and 90-min data significantly improved without affecting test-retest performance.This study suggests that a 15% change of SUVmean/SUVpeak at 60 min after injection can be used to assess response in advanced NSCLC patients if up to 5 PERCIST target lesions are assessed. Lower thresholds could be used in averaged PERCIST target lesions (<10%).
[18F]-FDG-PET/CT ([18F]-fluoro-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)) is increasingly used as a diagnostic tool in suspected infectious or inflammatory conditions. Studies on the value of FDG-PET/CT in children are scarce. This study assesses the role of FDG-PET/CT in suspected infection or inflammation in children. In this multicenter cohort study, 64 scans in 59 children with suspected infection or inflammation were selected from 452 pediatric FDG-PET/CT scans, performed in five hospitals between January 2016 and August 2017. Main outcomes were diagnostic information provided by FDG-PET/CT for diagnostic scans and impact on clinical management for follow-up scans. Of these 64 scans, 50 were performed for primary diagnosis and 14 to monitor disease activity. Of the positive diagnostic scans, 23/27 (85%) contributed to establishing a diagnosis. Of the negative diagnostic scans, 8/21 (38%) contributed to the final diagnosis by narrowing the differential or by providing information on the disease manifestation. In all follow-up scans, FDG-PET/CT results guided management decisions. CRP was significantly higher in positive scans than in negative scans (p = 0.004). In 6% of diagnostic scans, relevant incidental findings were identified. In conclusion, FDG-PET/CT performed in children with suspected infection or inflammation resulted in information that contributed to the final diagnosis or helped to guide management decisions in the majority of cases. Prospective studies assessing the impact of FDG-PET/CT results on diagnosis and patient management using a structured diagnostic protocol are feasible and necessary.
289 Objectives: We explored the possibility of using SUVpeak (defined as a 1mL sphere with the highest average SUV within a lesion/target) derived from 18F-FDG PET/CT images reconstructed with point-spread-function resolution modelling as a surrogate for SUVmax derived from images reconstructed with an EARL compliant protocol. SUVpeak was already suggested as being a better alternative than SUVmax when derived from PSF images1. This assessment was performed using phantom images and clinical data from stage III and IV non-small cell lung cancer (NSCLC) patients.
Methods
The National Electrical Manufacturers Association (NEMA) image quality phantom was scanned for 5 minutes with a 10:1 sphere-to-background contrast ratio. Additionally, ten stage III and IV NSCLC patients underwent two baseline 18F-FDG PET/CT scans per day at 60min and 90min post injection, at two separate time-points within one week2. All data were reconstructed following two protocols: one compliant with EANM guidelines (EARL multicentre standard) and another with point-spread-function (PSF) resolution modelling. The latter protocol allows for improved lesion detection, but does not provide EARL compliant quantitative results. Patients’ lesions were segmented using a semi-automatic isocontour at SUV=4.0 g/mL. NEMA spheres were manually delineated based on their diameter. The SUVpeak PSF-derived (SUVpeakPSF) was compared with SUVmax EARL-derived (SUVmaxEARL) with Pearson’s correlations, t-tests and Bland-Altman plots.
Results
For the phantom scans, the mean relative difference between SUVpeakPSF and SUVmaxEARL was -11.0% (SD=15.0%) and showed a correlation ρ=0.95. Considering only the three biggest spheres (volumes larger than 5 mL), the mean relative difference was 1.8% (SD=3.5%). The clinical dataset (total of 21 lesions analysed) presented similar results, with a perfect correlation between SUVpeakPSF and SUVmaxEARL (ρ=1.00) and a mean relative difference of -4.3% (SD=5.2%). This highlights that, overall, SUVpeakPSF values are slightly lower than SUVmaxEARL values. Only two lesions were identified as smaller than 5 mL using the EARL reconstruction, three with PSF. The relative difference between SUV implementations for those small lesions was -7.1% (SD=4.3%). Moreover, uptake time did not affect the differences seen between SUVpeakPSF and SUVmaxEARL, which were -4.2% (SD=5.0%) and -4.3% (SD=5.6%) for the 60 and 90 minutes post-injection data (p=0.89), respectively.
Conclusion
This pilot study suggests that SUVpeak derived from high resolution PSF reconstructed 18F-FDG PET/CT images might be used as a surrogate for SUVmaxEARL for lesions bigger than 5mL. Conclusions on smaller lesions cannot be substantiated due to limited sample size. Further research using data from different centres and on larger as well as different patient groups is required to fully evaluate the feasibility and clinical impact of using SUVpeakPSF as a surrogate for SUVmaxEARL.
References
1. Mansor, S., Pfaehler, E., Heijtel, D., et al. (2017), Impact of PET/CT system, reconstruction protocol, data analysis method, and repositioning on PET/CT precision: An experimental evaluation using an oncology and brain phantom. Med. Phys., 44, 6413-6424. doi:10.1002/mp.12623
2. Kramer, G. M., Frings, V., Hoetjes, N., et al. (2016). Repeatability of quantitative whole-body 18F-FDG PET/CT uptake measures as function of uptake interval and lesion selection in non-small cell lung cancer patients. Journal of Nuclear Medicine, 57(9), 1343-1349. doi:10.2967/jnumed.115.170225.
375 Objectives To validate multiple parametric methods for quantification of [18F]-Fluorothymidine PET ([18F]FLT PET) in patients with advanced EGFR mutation positive non-small cell lung carcinoma (NSCLC) treated with gefitinib, an EGFR tyrosine kinase inhibitor (TKI). Methods Ten NSCLC patients underwent dynamic [15O]H2O and [18F]FLT PET/CT at baseline, 7 and 28 days after start of treatment. Venous and arterial samples were collected during PET for metabolite correction of the image-derived input function. Parametric images were generated using plasma input Logan (LGA) and Patlak graphic analysis and two basis functions based methods: a 2-tissue compartment basis function model (BFM) and spectral analysis (SA). Whole tumor averaged parametric pharmacokinetic parameters were compared with those obtained by nonlinear regression (NLR) of the tumor time activity curve using a 2-tissue compartment reversible model with blood volume fraction1. Results After optimizing the settings of each parametric method, distribution volumes (VT) (Median: 3.46 And IQR: 2.0) obtained with LGA, BFM and SA all correlated well with those derived using NLR at baseline as well as during therapy (R2≥0.98, ICC>0.97 and Slope: 0.853, 1.00 and 1.09 resp. LGA, BFM and SA). BFM and SA also generated accurate K1 values compared with those from NLR analysis (R2: 0.989, ICC: 0.962, slope: 1.00 and R2: 0.980, ICC: 0.906, slope: 1.00 resp.). Patlak analysis did not provide quantitatively robust Ki values. Perfusion ( [15O]H2O) was not correlated to VT and K1 derived from the various parametric methods. Conclusions BFM can generate quantitative accurate parametric FLT VT images in NSCLC patients before and during therapy, while LGA and SA based VT showed some negative and positive bias respectively. Moreover, BFM provided quantitative accurate parametric K1 data. We therefore recommend BFM as the preferred parametric method for analysis of dynamic [18F]FLT PET/CT studies.
1517 Objectives Pharmacokinetic analysis of dynamic PET studies requires an accurate plasma input function. Image derived input functions (IDIFs) are an alternative to arterial input functions (AIFs) obtained from invasive and laborious arterial blood sampling. The aim of the present study was to assess the interobserver variability in manual definition of blood volumes of interest (VOI) for generating IDIFs and its effect on pharmacokinetic analysis results. Methods 10 non-small cell lung cancer patients were included. 5 patients underwent a dynamic 70 min [18F]FAZA PET scan along with continuous arterial blood sampling and 5 patients underwent a dynamic 60 min [18F]FLT PET scan. Arterial manual samples were taken. 6 observers manually defined VOIs within the ascending aorta (AA), the descending aorta, the left ventricle and the aortic arch (AArch) on each scan. IDIFs were derived both with and without calibration, metabolite and plasma-to-blood ratio correction. For each patient tumour time activity curves were fitted using a reversible two tissue compartment model. For each VOI and resulting IDIF, percentage error (PE) with the results of the observer with highest expertise was obtained for: size and location of the VOIs, the area under the curve (AUC) of the IDIFs, volume of distribution (Vt) and K1. PE of AUC and Vt obtained from IDIFs with those obtained from AIFs for FAZA were obtained. Results For FAZA corrected IDIFs showed least PE from AIFs as compared to uncorrected IDIFs (avg of Conclusions Best correspondence with AIF was obtained with corrected IDIFs. Moderate interobserver variability was found for manually defined IDIFs. With corrected IDIFs VOI AA and with uncorrected IDIFs VOI AArch showed best correspondence. Automated VOI definition could eliminate variability and outliers. Research Support Funded by the QuIC-ConCePT project of IMI
Objectives Pemetrexed is a thymidylate synthase (TS) inhibitor and is effective in non-small cell lung cancer (NSCLC). 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), a proliferation marker, could potentially identify tumor specific TS-inhibition. The aim of this study was to investigate the effect of pemetrexed-induced TS-inhibition on 18F-FLT uptake 4 hours after pemetrexed administration in metastatic NSCLC patients. Methods Fourteen NSCLC patients underwent dynamic 18F-FLT positron emission tomography (PET) scans at baseline and 4 hours after the first dose of pemetrexed. Volumes of interest were defined with a 41%, 50% and 70% threshold of the maximum pixel. Kinetic analysis and simplified measures were performed. At one, two, four and six hours after pemetrexed, plasma deoxyuridine was measured as systemic indicator of TS-inhibition. Tumor response measured with response evaluation criteria in solid tumors (RECIST), time to progression (TTP) and overall survival (OS) were determined. Results Eleven patients had evaluable 18F-FLT PET scans at baseline and 4 hours after pemetrexed. Two patients had increased 18F-FLT uptake of 35% and 31% after pemetrexed, whereas two other patients had decreased uptake of 31%. In the remaining seven patients 18F-FLT uptake did not change beyond test-retest borders. In all patients deoxyuridine levels raised after administration of pemetrexed, implicating pemetrexed-induced TS-inhibition. 18F-FLT uptake in bone marrow was significantly increased 4 hours after pemetrexed administration. Six weeks after the start of treatment 5 patients had partial response, 4 stable disease and 2 progressive disease. Median TTP was 4.2 months (range 3.0–7.4 months); median OS was 13.0 months (range 5.1–30.8 months). Changes in 18F-FLT uptake were not predictive for tumor response, TTP or OS. Conclusions Measuring TS-inhibition in a clinical setting 4 hours after pemetrexed revealed a non-systematic change in 18F-FLT uptake within the tumor. No significant association with tumor response, TTP or OS was observed.
3′-deoxy-3′-18F-fluorothymidine (18F-FLT) PET/CT provides a noninvasive assessment of proliferation and, as such, could be a valuable imaging biomarker in oncology. The aim of the present study was to assess the validity of simplified quantitative parameters of 18F-FLT uptake in non–small cell lung cancer (NSCLC) patients before and after the start of treatment with a tyrosine kinase inhibitor (TKI). Methods: Ten patients with metastatic NSCLC harboring an activating epidermal growth factor receptor mutation were included in this prospective observational study. Patients underwent 15O-H2O and 18F-FLT PET/CT scanning on 3 separate occasions: within 7 d before treatment, and 7 and 28 d after the first therapeutic dose of a TKI (gefitinib or erlotinib). Dynamic scans were acquired and venous blood samples were collected during the 18F-FLT scan to measure parent fraction and plasma and whole-blood radioactivity concentrations. Simplified measures (standardized uptake value [SUV] and tumor-to-blood ratio [TBR]) were correlated with fully quantitative measures derived from kinetic modeling. Results: Twenty-nine of thirty 18F-FLT PET/CT scans were evaluable. According to the Akaike criterion, a reversible 2-tissue model with 4 rate constants and blood volume parameter was preferred in 84% of cases. Relative therapy-induced changes in SUV and TBR correlated with those derived from kinetic analyses (r2 = 0.83–0.97, P < 0.001, slope = 0.72–1.12). 18F-FLT uptake significantly decreased at 7 and 28 d after the start of treatment compared with baseline (P < 0.01). Changes in 18F-FLT uptake were not correlated with changes in perfusion, as measured using 15O-H2O. Conclusion: SUV and TBR could both be used as surrogate simplified measures to assess changes in 18F-FLT uptake in NSCLC patients treated with a TKI, at the cost of a small underestimation in uptake changes or the need for a blood sample and metabolite measurement, respectively.
Accurate quantification of tracer uptake in small tumors using PET is hampered by the partial-volume effect as well as by the method of volume-of-interest (VOI) delineation. This study aimed to investigate the effect of partial-volume correction (PVC) combined with several VOI methods on the accuracy and precision of quantitative PET.Four image-based PVC methods and resolution modeling (applied as PVC) were used in combination with several common VOI methods. Performance was evaluated using simulations, phantom experiments, and clinical repeatability studies. Simulations were based on a whole-body 18F-FDG PET scan in which differently sized spheres were placed in lung and mediastinum. A National Electrical Manufacturers Association NU2 quality phantom was used for the experiments. Repeatability data consisted of an 18F-FDG PET/CT study on 11 patients with advanced non-small cell lung cancer and an 18F-fluoromethylcholine PET/CT study on 12 patients with metastatic prostate cancer.Phantom data demonstrated that most PVC methods were strongly affected by the applied resolution kernel, with accuracy differing by about 20%-50% between full-width-at-half-maximum settings of 5.0 and 7.5 mm. For all PVC methods, large differences in accuracy were seen among all VOI methods. Additionally, the image-based PVC methods were observed to have variable sensitivity to the accuracy of the VOI methods. For most PVC methods, accuracy was strongly affected by more than a 2.5-mm misalignment of true (simulated) VOI. When the optimal VOI method for each PVC method was used, high accuracy could be achieved. For example, resolution modeling for mediastinal lesions and iterative deconvolution for lung lesions were 99% ± 1.5% and 99% ± 0.9% accurate, respectively, for spheres 15-40 mm in diameter. Precision worsened slightly for resolution modeling and to a larger extent for some image-based PVC methods. Uncertainties in delineation propagated into uncertainties in PVC performance, as confirmed by the clinical data.The accuracy and precision of the tested PVC methods depended strongly on VOI method, resolution settings, contrast, and spatial alignment of the VOI. PVC has the potential to substantially improve the accuracy of tracer uptake assessment, provided that robust and accurate VOI methods become available. Commonly used delineation methods may not be adequate for this purpose.
