Dose-Finding Quantitative <sup>18</sup>F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies

Gungor, Hatice; Saleem, Azeem; Babar, Syed; Dina, Roberto; El‐Bahrawy, Mona; Curry, Ed; Rama, Nona; Chen, Michele; Pickford, Emily; Agarwal, Roshan; Blagden, Sarah P.; Carme, Sabin; Salinas, Cristian; Madison, Sam J; Krachey, Elizabeth C.; Santiago-Walker, Ademi; Smith, Deborah A.; Morris, Shannon R.; Stronach, Euan A.; Gabra, Hani

doi:10.2967/jnumed.115.156505

Cited by 26 publications

(22 citation statements)

References 28 publications

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“…Regarding reproducibility or robustness, it has been shown that only a few features are robust with regard to variations in the type of image reconstruction algorithm [24, 52, 74, 80]. It has also shown that the effects of tumour segmentation [52, 57, 58, 75], postreconstruction smoothing [26], quantization [52, 58] and partial volume effect correction [75] vary among TA metrics.…”

Section: Repeatability and Reproducibility/robustnessmentioning

confidence: 99%

“…This would allow major issues in comparing co-occurrence-derived metrics calculated with different spatial sampling to be avoided [55, 74]. Second, avoid postreconstruction smoothing altogether, or use appropriate edge-preserving filters [26]. Third, automated segmentation approaches with robustness against heterogeneous distributions should be used [61, 66].…”

Section: Conclusion: a Future For Texture Analysis In Pet?mentioning

confidence: 99%

“…PET images have a priori less-favourable properties for TA than MRI or CT, due to a lower signal-to-noise ratio and spatial resolution, as well as poorer spatial sampling. In addition, reconstructed PET images are often smoothed in clinical practice for visual analysis by clinicians using filters which reduce the textural content of the image, such as the gaussian filter [26]. However, the fidelity and quantitative accuracy of PET imaging has substantially improved in the last decade, with the advent of PET/CT systems, time-of-flight (TOF) capabilities, improved sensitivity, and the incorporation of several quantitative corrections in the current clinical gold standard iterative reconstruction algorithms [27].…”

Section: Introductionmentioning

confidence: 99%

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Characterization of PET/CT images using texture analysis: the past, the present… any future?

Hatt

Tixier

Pierce

et al. 2016

Eur J Nucl Med Mol Imaging

413

383

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After seminal papers over the period 2009 – 2011, the use of texture analysis of PET/CT images for quantification of intratumour uptake heterogeneity has received increasing attention in the last 4 years. Results are difficult to compare due to the heterogeneity of studies and lack of standardization. There are also numerous challenges to address. In this review we provide critical insights into the recent development of texture analysis for quantifying the heterogeneity in PET/CT images, identify issues and challenges, and offer recommendations for the use of texture analysis in clinical research. Numerous potentially confounding issues have been identified, related to the complex workflow for the calculation of textural features, and the dependency of features on various factors such as acquisition, image reconstruction, preprocessing, functional volume segmentation, and methods of establishing and quantifying correspondences with genomic and clinical metrics of interest. A lack of understanding of what the features may represent in terms of the underlying pathophysiological processes and the variability of technical implementation practices makes comparing results in the literature challenging, if not impossible. Since progress as a field requires pooling results, there is an urgent need for standardization and recommendations/guidelines to enable the field to move forward. We provide a list of correct formulae for usual features and recommendations regarding implementation. Studies on larger cohorts with robust statistical analysis and machine learning approaches are promising directions to evaluate the potential of this approach.

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Section: Repeatability and Reproducibility/robustnessmentioning

confidence: 99%

Section: Conclusion: a Future For Texture Analysis In Pet?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of PET/CT images using texture analysis: the past, the present… any future?

Hatt

Tixier

Pierce

et al. 2016

Eur J Nucl Med Mol Imaging

413

383

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“…The functional consequences of therapeutic interventions as assessed by RPPAs are providing early signals to identify patients who will benefit from continued treatment with a particular intervention 42, 43 and those who may benefit from the addition of another agent or switching to an alternative therapy. One of the most exciting uses of pharmacodynamic analysis of adaptive response is in elucidating feedback and feed-forward loops as well as homeostatic processes.…”

Section: Uses Of Rppa Technologymentioning

confidence: 99%

Using reverse-phase protein arrays as pharmacodynamic assays for functional proteomics, biomarker discovery, and drug development in cancer

Ling

Hegde

et al. 2016

Seminars in Oncology

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The majority of the targeted therapeutic agents in clinical use target proteins and protein function. Although DNA and RNA analyses have been used extensively to identify novel targets and patients likely to benefit from targeted therapies, these are indirect measures of the levels and functions of most therapeutic targets. More importantly, DNA and RNA analysis is ill-suited for determining the pharmacodynamic effects of target inhibition. Assessing changes in protein levels and function is the most efficient way to evaluate the mechanisms underlying sensitivity and resistance to targeted agents. Understanding these mechanisms is necessary to identify patients likely to benefit from treatment and to develop rational drug combinations to prevent or bypass therapeutic resistance. There is an urgent need for a robust approach to assess protein levels and protein function in model systems and across patient samples. While “shot gun” mass spectrometry can provide in-depth analysis of proteins across a limited number of samples, and emerging approaches such as multiple reaction monitoring have the potential to analyze candidate markers, mass spectrometry has not entered into general use because of the high cost, requirement of extensive analysis and support, and relatively large amount of material needed for analysis. Rather, antibody-based technologies, including immunohistochemistry, radio immunoassays, ELISAs and more recently protein arrays, remain the most common approaches for multiplexed protein analysis. Reverse-phase protein array (RPPA) technology has emerged as a robust, sensitive, cost-effective approach to the analysis of large numbers of samples for quantitative assessment of key members of functional pathways that are affected by tumor-targeting therapeutics. The RPPA platform is a powerful approach for identifying and validating targets, classifying tumor subsets, assessing pharmacodynamics, and identifying prognostic and predictive markers, adaptive responses and rational drug combinations in model systems and patient samples. Its greatest utility has been realized through integration with other analytic platforms such as DNA sequencing, transcriptional profiling, epigenomics, mass spectrometry, and metabolomics. The power of the technology is becoming apparent through its use in pathology laboratories and integration into trial design and implementation.

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“…Along these lines, Vallius et al used 18 F-FDG PET/CT to predict histopathologic responders and nonresponders to neoadjuvant chemotherapy before interval debulking surgery (18). In another example, a recent clinical study in 12 platinum-resistant patients demonstrated an exposure–response relationship between a pan-Akt inhibitor and the tumoral uptake of 18 F-FDG (19). …”

Section: Nuclear Imagingmentioning

confidence: 99%

Molecular Imaging of Ovarian Cancer

et al. 2016

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Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this “Focus on Molecular Imaging” review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering recent advances in the MR, PET, SPECT, ultrasound, and optical imaging of ovarian cancer. Although primary emphasis is given to clinical studies, preclinical investigations that are particularly innovative and promising are discussed as well. Ultimately, we are hopeful that the combination of technologic innovations, novel imaging probes, and further integration of imaging into clinical protocols will lead to significant improvements in the survival rate for ovarian cancer.

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Dose-Finding Quantitative ¹⁸F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies

Cited by 26 publications

References 28 publications

Characterization of PET/CT images using texture analysis: the past, the present… any future?

Characterization of PET/CT images using texture analysis: the past, the present… any future?

Using reverse-phase protein arrays as pharmacodynamic assays for functional proteomics, biomarker discovery, and drug development in cancer

Molecular Imaging of Ovarian Cancer

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Dose-Finding Quantitative 18F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies

Cited by 26 publications

References 28 publications

Characterization of PET/CT images using texture analysis: the past, the present… any future?

Characterization of PET/CT images using texture analysis: the past, the present… any future?

Using reverse-phase protein arrays as pharmacodynamic assays for functional proteomics, biomarker discovery, and drug development in cancer

Molecular Imaging of Ovarian Cancer

Contact Info

Product

Resources

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Dose-Finding Quantitative ¹⁸F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies