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Impact of the definition of peak standardized uptake value on quantification of treatment response.

ABSTRACT: PET-based treatment response assessment typically measures the change in maximum standardized uptake value (SUV(max)), which is adversely affected by noise. Peak SUV (SUV(peak)) has been recommended as a more robust alternative, but its associated region of interest (ROI(peak)) is not uniquely defined. We investigated the impact of different ROI(peak) definitions on quantification of SUV(peak) and tumor response.Seventeen patients with solid malignancies were treated with a multitargeted receptor tyrosine kinase inhibitor resulting in a variety of responses. Using the cellular proliferation marker 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), whole-body PET/CT scans were acquired at baseline and during treatment. (18)F-FLT-avid lesions (?2/patient) were segmented on PET images, and tumor response was assessed via the relative change in SUV(peak). For each tumor, 24 different SUV(peaks) were determined by changing ROI(peak) shape (circles vs. spheres), size (7.5-20 mm), and location (centered on SUV(max) vs. placed in highest-uptake region), encompassing different definitions from the literature. Within each tumor, variations in the 24 SUV(peaks) and tumor responses were measured using coefficient of variation (CV), standardized deviation (SD), and range. For each ROI(peak) definition, a population average SUV(peak) and tumor response were determined over all tumors.A substantial variation in both SUV(peak) and tumor response resulted from changing the ROI(peak) definition. The variable ROI(peak) definition led to an intratumor SUV(peak) variation ranging from 49% above to 46% below the mean (CV, 17%) and an intratumor SUV(peak) response variation ranging from 49% above to 35% below the mean (SD, 9%). The variable ROI(peak) definition led to a population average SUV(peak) variation ranging from 24% above to 28% below the mean (CV, 14%) and a population average SUV(peak) response variation ranging from only 3% above to 3% below the mean (SD, 2%). The size of ROI(peak) caused more variation in intratumor response than did the location or shape of ROI(peak). Population average tumor response was independent of size, shape, and location of ROI(peak).Quantification of individual tumor response using SUV(peak) is highly sensitive to the ROI(peak) definition, which can significantly affect the use of SUV(peak) for assessment of treatment response. Clinical trials are necessary to compare the efficacy of SUV(peak) and SUV(max) for quantification of response to therapy.

SUBMITTER: Vanderhoek M

PROVIDER: S-EPMC3308343 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Impact of the definition of peak standardized uptake value on quantification of treatment response.

Vanderhoek Matt M Perlman Scott B SB Jeraj Robert R

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20120101 1

<h4>Unlabelled</h4>PET-based treatment response assessment typically measures the change in maximum standardized uptake value (SUV(max)), which is adversely affected by noise. Peak SUV (SUV(peak)) has been recommended as a more robust alternative, but its associated region of interest (ROI(peak)) is not uniquely defined. We investigated the impact of different ROI(peak) definitions on quantification of SUV(peak) and tumor response.<h4>Methods</h4>Seventeen patients with solid malignancies were t ...[more]

PMID: 22213818

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Project description:Axial spondyloarthritis is a chronic inflammatory rheumatic disease that affects the axial skeleton and causes severe pain and disability. It may be also associated with extra-articular manifestations. Early diagnosis and appropriate treatment can reduce the severity of the disease and the risk of progression. The biological disease-modifying antirheumatic drugs (bDMARDs) tumor necrosis factor alpha (TNFα) inhibitors (TNFi) and the anti-interleukin (IL)-17A antibodies secukinumab and ixekizumab are effective agents to reduce disease activity and minimize the inflammation that damages the joints. New alternatives such as Janus kinase (JAK) inhibitors are also available. Unfortunately, response rates to bDMARDs are far from optimal, and many patients experience so-called treatment failure. The definition of treatment failure definition is often vague and may depend on the rigorousness of the therapeutic goal, the inclusion or not of peripheral symptoms/extra-articular manifestations, or patients' overall health. After an exhaustive bibliographic review, we propose a definition based on loss of the following status: low disease activity assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, absence of extra-articular manifestations, and low disease impact on the patients' general health. Apart from discontinuing the therapy because of safety or intolerance reasons, two types of treatment failure can be differentiated depending on when it occurs: primary failure (no response within 6 months after treatment initiation, or lack of efficacy) and secondary failure (response within 6 months but lost thereafter, or loss of efficacy over time). Physicians should carefully consider the moment and the reason for the treatment failure to decide the next therapeutic step. In the case of primary failure on a first TNFi, it seems reasonable to switch to another class of drugs, i.e., an anti-IL-17 agent, as phase III trials showed that the response to IL-17 blockade was higher than to placebo in patients previously exposed to TNFi. When secondary failure occurs, and loss of efficacy is suspected to be caused by antidrug antibodies (ADAs), it is advisable to analyze serum TNFi and ADAs concentrations, if possible; in the presence of ADAs and low TNFi levels, changing the TNFi is rational as it may restore the TNFα blocking capacity. If ADAs are absent/low with adequate drug therapeutic levels, switching to another target might be the best strategy.

Project description:PurposePredictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT).Patients and methodsPatients with stage II/III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%.ResultsEighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed.ConclusionEarly changes in SULmax predict response to four cycles of PT in estrogen receptor-negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.

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Project description:PurposeTumor response assessments on positron emission tomography (PET)/magnetic resonance imaging (MRI) scans require correct quantification of radiotracer uptake in tumors and normal organs. Historically, MRI scans have been enhanced with gadolinium (Gd)-based contrast agents, which are now controversial due to brain deposition. Recently, ferumoxytol nanoparticles have been identified as an alternative to Gd-based contrast agents because they provide strong tissue enhancement on MR images but are not deposited in the brain. However, it is not known if the strong T1- and T2-contrast obtained with iron oxide nanoparticles such as ferumoxytol could affect MR-based attenuation correction of PET data. The purpose of our study was to investigate if ferumoxytol administration prior to a 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG PET/MR scan would change standardized uptake values (SUV) of normal organs.ProceduresThirty pediatric patients (6-18 years) with malignant tumors underwent [18F]FDG-PET/MR scans (dose 3 MBq/kg). Fifteen patients received an intravenous ferumoxytol injection (5 mg Fe/kg) prior to the [18F]FDG-PET/MR scans (group 1). Fifteen additional age- and sex-matched patients received unenhanced [18F]FDG-PET/MR scans (group 2). For attenuation correction of PET data, we used a Dixon-based gradient echo sequence (TR 4.2 ms, TE 1.1, 2.3 ms, FA 5), which accounted for soft tissue, lung, fat, and background air. We used a mixed linear effects model to compare the tissue MRI enhancement, quantified as the signal-to-noise ratio (SNR), as well as tissue radiotracer signal, quantified as SUVmean and SUVmax, between group 1 and group 2. Alpha was assumed at 0.05.ResultsThe MRI enhancement of the blood and solid extra-cerebral organs, quantified as SNR, was significantly higher on ferumoxytol-enhanced MRI scans compared to unenhanced scans (p < 0.001). However, SUVmean and SUVmax values, corrected based on the patients' body weight or body surface area, were not significantly different between the two groups (p > 0.05).ConclusionFerumoxytol administration prior to a [18F]FDG PET/MR scan did not change standardized uptake values (SUV) of solid extra-cerebral organs. This is important, because it allows injection of ferumoxytol contrast prior to a PET/MRI procedure and, thereby, significantly accelerates image acquisition times.

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Impact of the definition of peak standardized uptake value on quantification of treatment response.

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Impact of the definition of peak standardized uptake value on quantification of treatment response.

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