Introduction Cerebral metastases are the most common intracranial tumors in adults and occur in approximately 15–25 % of all cancer patients. Stereotactic radiosurgery (SRS) is a non-invasive alternative to surgical resection of brain metastasis^[1]. There has not been an established radiological criteria on evaluating the response of brain metastases to SRS in the early post-treatment period. Therefore, an imaging method that could be used to detect early tumor response would be helpful in identifying the true early response of the tumor after SRS treatment.

Purpose

Dynamic contrast-enhanced (DCE) MRI provides additional information regarding blood-brain barrier integrity, and K^trans is directly proportional to the level of permeability of the blood-brain barrier^[2]. The purpose of this study was to evaluate the effect of SRS on cerebral metastases using K^trans derived from DCE MRI and to explore the ability of K^trans measurements on predicting midterm tumor outcomes after SRS^[3].

Materials and Methods

All patients underwent a single high-dose SRS performed using a Clinac 6EX photon linear accelerator (Varian, Palo Alto, CA, USA). Seven patients received whole-brain radiation therapy prior to SRS with a mean dose of 3,000 cGy divided into ten fractions. MRI was performed in Optima MR360 (General Electric Medical Systems, Waukesha, WI, USA). DCE MRI was added to the usual brain tumor protocols using a spoiled gradient-echo acquisition. Fifty dynamic phases were obtained with a temporal sampling interval of 6s and a total imaging time of 6.1 min. The bolus injection of 0.1 mmol/Kg of the contrast agent was administered after the second set of dynamic images at a rate of 2.5 mL/s. DCE MRI data were then processed. Parametric maps were used to measure K^trans at the regions of interest (ROIs), and the highest (maximum) values were used for analysis, the tumor volumes were subsequently calculated. All statistical analyses were performed with SPSS 19.0. Relationship between K^trans and tumor volume was assessed using Spearman’s rank correlation coefficient, and hazard ratios (HRs) for the association between K^trans and midterm tumor progression were obtained using Cox proportional hazard models.

Results

K^trans of the metastatic lesions presented a significant reduction after SRS treatment. The mean (±SD) K^trans value was 0.13±0.11 min^-1 at the baseline and 0.08±0.07 min^-1 at the early post treatment follow-up (p<0.001). There was a significant positive correlation between K^trans ratio and tumor growth ratio (Spearman’s coefficient=0.58, p=0.005)(Tab.1). The mean baseline K^trans values were not significantly correlated with the mean midterm tumor volumes. An increase in K^trans ratio was significantly associated with lesion progression. Each unit increase in K^trans ratio after SRS was associated with an additional risk of 50 % of tumor progression (HR=1.50, 95 % CI=1.16–1.70, p<0.001)(Fig.1). K^trans ratio showed a sensitivity of 78 % and a specificity of 85 % with a cutoff of 0.15 (increase of 15 %) for predicting midterm lesion outcomes(Fig.2).

Conclusion

SRS of cerebral metastasis is associated with a decrease of K^trans values in the early post-treatment period. Furthermore, K^trans variation is predictive of midterm tumor outcome. These results suggest that DCE MRI K^trans is a valuable biomarker to evaluate treatment responses in the early post-SRS period during which the identification of treatment failure is more critical. Further large-scale studies may provide a proof of the potential capability of this new method and could also evaluate its performance while combined with other MRI techniques.

Acknowledgements

No acknowledgement found.

References

[1]. Rahman M, Cox JB, Chi YY et al. Radiographic response of brain metastasis after linear accelerator radiosurgery. Stereotact Funct Neurosurg 2012; 90:69–78.
[2]. Thompson G, Mills SJ, Stivaros SM, Jackson A. Imaging of brain tumors: perfusion/permeability. Neuroimaging Clin N Am 2010; 20:337–353.
[3]. Peng SL, Chen CF, Liu HL, et al. Analysis of parametric histogram from dynamic contrast-enhanced MRI: application in evaluating brain tumor response to radiotherapy. NMR Biomed 2012.