The ideal method for non-invasive monitoring of biological or metabolic activity in the brainstem has not yet been established. Existing methods for evaluating cerebral tissue (e.g. PET) have limitations when applied to the brainstem. New noninvasive imaging methods are currently being studied. We are using dynamic susceptibility contrast MR perfusion, dynamic enhanced MRI, proton nuclear magnetic spectroscopic imaging, and FDG PET to further investigate the imaging characteristics of pontine gliomas. There are four clinical trials which currently fall under this project. Nearly all pediatric patients with CNS tumors undergo extensive imaging on at least one of these studies. Over the past year, we have demonstrated the difficulty in using standard MRI for definition of response in clinical trials and have proposed a new definition of clinical benefit for these patients based on these results. Response to treatment and therefore efficacy of new gents is typically measured using two-dimensional tumor measurements following WHO criteria, or more recently, using RECIST criteria. RECIST criteria have not been validated for the measurement of pediatric CNS tumors and two-dimensional measurements continue to be the standard in consortium trials. We compared the 1D, 2D and 3D measurements of diffuse intrinsic pontine gliomas by four separate blinded readers. The results show that there is significant variability (0-197%) in all measurements and change in tumor size is therefore a poor indicator of response for clinical trials. We have also electronically surveyed pediatric oncologists and neuro-oncologists across the country to determine the standard practice of tumor measurement. Our results show that there is no standard measurement method being used in the measurement of these lesions. We have published a report recommending the use of FLAIR images to measure DIPG and comparing these with the best response scans on study. Images should be compared side by side. Central review was also recommended for clinical trials involving DIPG. We are continuing to evaluate the utility of additional MR sequences, including perfusion and spectroscopic imaging in an attempt to define the role of specific imaging techniques (e.g. spectroscopy, PET) in these patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010589-06
Application #
7965439
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2009
Total Cost
$198,668
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Steffen-Smith, Emilie A; Baker, Eva H; Venzon, David et al. (2014) Measurements of the pons as a biomarker of progression for pediatric DIPG. J Neurooncol 116:127-33
Hipp, Sean J; Steffen-Smith, Emilie A; Patronas, Nicholas et al. (2012) Molecular imaging of pediatric brain tumors: comparison of tumor metabolism using ยน?F-FDG-PET and MRSI. J Neurooncol 109:521-7
Steffen-Smith, Emilie A; Venzon, David J; Bent, Robyn S et al. (2012) Single- and multivoxel proton spectroscopy in pediatric patients with diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 84:774-9
Ko, Christine; Kaushal, Aradhana; Hammoud, Dima A et al. (2012) Role of early postradiation magnetic resonance imaging scans in children with diffuse intrinsic pontine glioma. Int J Radiat Oncol Biol Phys 83:1252-1256
Steffen-Smith, Emilie A; Shih, Joanna H; Hipp, Sean J et al. (2011) Proton magnetic resonance spectroscopy predicts survival in children with diffuse intrinsic pontine glioma. J Neurooncol 105:365-73
Hipp, Sean J; Steffen-Smith, Emilie; Hammoud, Dima et al. (2011) Predicting outcome of children with diffuse intrinsic pontine gliomas using multiparametric imaging. Neuro Oncol 13:904-9
Kim, Aerang; Fox, Elizabeth; Warren, Katherine et al. (2008) Characteristics and outcome of pediatric patients enrolled in phase I oncology trials. Oncologist 13:679-89
Hayward, Robert M; Patronas, Nicolas; Baker, Eva H et al. (2008) Inter-observer variability in the measurement of diffuse intrinsic pontine gliomas. J Neurooncol 90:57-61