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  • Magnetic resonance imaging-based tumour perfusion parameters are biomarkers predicting response after radiation to brain metastases.

Magnetic resonance imaging-based tumour perfusion parameters are biomarkers predicting response after radiation to brain metastases.

Clinical oncology (Royal College of Radiologists (Great Britain)) (2014-07-16)
R Jakubovic, A Sahgal, H Soliman, R Milwid, L Zhang, A Eilaghi, R I Aviv
ABSTRACT

To investigate whether early relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and permeability (Ktrans(2)) measurements may serve as magnetic resonance imaging (MRI) biomarkers of radiation response or progression for brain metastases. Seventy brain metastases in 44 patients treated with either stereotactic radiosurgery or whole brain radiotherapy were imaged with dynamic susceptibility and dynamic contrast enhancement MRI at baseline, 1 week and 1 month after treatment. The final response status was determined according to volume criteria derived from a 1 year post-treatment MRI or last available follow-up MRI. Tumours were characterised as responders, non-responders, progressors and non-progressors and compared for Ktrans(2), rCBF and rCBV differences. Uni- and multivariate analysis evaluated factors associated with tumour response and progression at 1 week and 1 month. A generalised estimating equations (GEE) model accounted for multiple tumours per subject. Receiver operator characteristic (ROC) analysis identified optimal cut-off values, sensitivity and specificity for response or progression. Tumour responders showed lower Ktrans(2) and reduced rCBF at 1 week (P < 0.05 each). Progressive disease showed lower rCBF and reduced rCBV at 1 month (P < 0.05 each). GEE and multivariate analysis revealed lower Ktrans(2) at 1 week, an absence of prior radiation predicted response. At 1 month only lower rCBV predicted progressive disease on GEE and multivariate analysis. Optimal cut-off points for Ktrans(2) and rCBV were 1.37 and 2.03 with sensitivity and specificity of 61.5 and 81.1% and 73.9 and 81.8%, respectively. Lower Ktrans(2) at 1 week and rCBV at 1 month discriminated responders and progressive disease, respectively.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Suplatast tosylate, ≥98% (HPLC)
Sigma-Aldrich
N,N′-Disuccinimidyl carbonate, purum, ≥95.0% (NMR)
Sigma-Aldrich
N,N′-Disuccinimidyl carbonate, ≥95%
Sigma-Aldrich
Gadolinium, chips
Sigma-Aldrich
Gadolinium, −40 mesh, 99% trace rare earth metals basis