Water Exchange Rate Constant as a Biomarker of Treatment Efficacy in Patients with Brain Metastases Undergoing Stereotactic Radiosurgery

Publication date: Available online 10 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hatef Mehrabian, Kimberly L. Desmond, Sofia Chavez, Colleen Bailey, Radoslaw Rola, Arjun Sahgal, Gregory J. Czarnota, Hany Soliman, Anne L. Martel, Greg J. Stanisz
PurposeThe use of stereotactic radiosurgery (SRS) for the treatment of patients with a few brain metastases has been increasing in clinical practice. Standard anatomical imaging is limited in its ability to evaluate treatment response early after treatment. It can take months before it is clear that a tumor has responded to SRS or not. This study was designed to evaluate if changes in the tumor after SRS can be seen with quantitative MRI early after the treatment.Methods and MaterialsUsing contrast enhanced MRI, a three water compartment tissue model consisting of intracellular (I), extracellular-extravascular (E), and vascular (V) compartments was employed to assess the intra-extracellular water exchange rate constant (kIE), efflux rate constant (kep) and water compartment volume fractions (M0,I,M0,E,M0,V). In this prospective study, 19 patients were MRI-scanned pre-treatment, one-week, and one-month after SRS. The change in model parameters between the pre-treatment and one-week post-treatment scans was correlated to the change in tumor volume between pre-treatment and one-month post-treatment scans.ResultsAt one-week kIE differentiated (p<0.001) tumors that had a partial response (PR) from stable and progressive disease (SD and PD) and a high correlation (R=−0.76,p<0.001) was observed between early changes in thekIE and tumor volume change one-month post-treatment. Other model parameters had lower correlation (M0,E) or no correlation (kep,M0,V).ConclusionsThis is the first study that measured kIE early after SRS, and found that early changes in kIE (one-week after treatment) highly correlated with long term tumor response and could predict the extent of tumor shrinkage at one-month post-SRS.

Teaser

Cells undergoing apoptosis experience increased intracellular to extracellular water exchange rate. A water exchange quantification technique for clinical DCE-MRI was developed and applied to 19 brain metastases patients treated with stereotactic radiosurgery (SRS). The intra-extracellular water exchange rate identified partial response patient within one-week after treatment, and also predicting the extent of tumor shrinkage at one month. Thus, intra-extracellular water exchange rate is a promising biomarker of brain metastases response to SRS.


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