Evaluation of Glioblastoma (GBM) Response to Therapy with Chemical Exchange Saturation Transfer (CEST)

Publication date: Available online 4 April 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hatef Mehrabian, Sten Myrehaug, Hany Soliman, Arjun Sahgal, Greg J. Stanisz
PurposeTo monitor cellular and metabolic characteristics of glioblastoma (GBM) over the course of standard 6-week chemo-radiation treatment with chemical exchange saturation transfer (CEST)-MRI, and identify the earliest time point CEST could determine subsequent therapeutic response.MethodsNineteen patients with newly diagnosed GBM were recruited and CEST-MRI was acquired immediately before (Day0), two weeks (Day14) and four weeks (Day28) into treatment, and one month after the end of treatment (Day70). Several CEST metrics including: magnetization transfer ratio and area under the curve of CEST peaks corresponding to nuclear overhauser effect (NOE), and amide protons (MTRNOE, MTRAmide, CESTNOE, CESTAmide respectively), magnetization transfer (MT), and direct water effect were investigated. Lack of early progression was determined as no increase in tumor size or worsening of clinical symptoms based on routine post chemo-radiation serial structural MRI.ResultsChanges in MTRNOE (Non-progressors=1.35±0.18, Progressors=0.97±0.22, p=0.006) and MTRAmide (Non-progressors=1.25±0.17, Progressors=0.99±0.10, p=0.017) between baseline (Day0) and Day14 resulted in the best separation of non-progressors from progressors. Moreover, the baseline (Day0) MTRNOE (Non-progressors=6.5±1.6[%], Progressors=9.1±2.1[%], p=0.015), MTRAmide (Non-progressors=6.7±1.7[%], Progressors=8.9±1.9[%], p=0.028), MT (Non-progressors=3.8±0.9[%], Progressors=5.4±1.4[%], p=0.019), and CESTNOE (Non-progressors=4.1±1.7[%·Hz], Progressors=6.1±1.9[%·Hz], p=0.044) were able to identify progressors even before the start of the treatment.ConclusionsCEST provides imaging-based biomarkers of GBM response as early as two weeks into the treatment. Certain CEST metrics can characterize tumor aggressiveness and identify early progressors even before beginning the treatment. Such early biomarker of response may allow for adjusting GBM treatment plan for adaptive radiotherapy in early progressors and more confidently continuing standard adjuvant treatment for non-progressors.

Teaser

Early determination of Glioblastoma (GBM) response to standard 6-week chemo-radiation may allow for adjusting subsequent therapy in non-responders. Chemical exchange saturation transfer (CEST) probes cellular and metabolic characteristics of the tumor which are more sensitive to treatment-induced changes (compared to tumor size change). CEST was able to identify those tumors that would progress early after treatment completion based on the imaging acquired as early as two weeks into the treatment course. Moreover, certain CEST metrics were able to characterize GBM aggressiveness even before treatment.


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